132-521: 2GL7 , 2VP7 , 2VPB , 2VPD , 2VPE , 2VPG , 3SL9 607 77578 ENSG00000116128 ENSMUSG00000038256 O00512 Q9D219 NM_004326 NM_029933 NP_004317 NP_084209 B-cell CLL/lymphoma 9 protein is a protein that in humans is encoded by the BCL9 gene . BCL9, together with its paralogue gene BCL9L (BCL9 like or BCL9.2), have been extensively studied for their role as transcriptional beta-catenin cofactors, fundamental for
264-516: A carboxyl group, and a variable side chain are bonded . Only proline differs from this basic structure as it contains an unusual ring to the N-end amine group, which forces the CO–NH amide moiety into a fixed conformation. The side chains of the standard amino acids, detailed in the list of standard amino acids , have a great variety of chemical structures and properties; it is the combined effect of all of
396-470: A gene may be duplicated before it can mutate freely. However, this can also lead to complete loss of gene function and thus pseudo-genes . More commonly, single amino acid changes have limited consequences although some can change protein function substantially, especially in enzymes . For instance, many enzymes can change their substrate specificity by one or a few mutations. Changes in substrate specificity are facilitated by substrate promiscuity , i.e.
528-423: A causal relationship between smoking and coronal caries, but evidence does suggest a relationship between smoking and root-surface caries. Exposure of children to secondhand tobacco smoke is associated with tooth decay. Intrauterine and neonatal lead exposure promote tooth decay. Besides lead, all atoms with electrical charge and ionic radius similar to bivalent calcium , such as cadmium , mimic
660-439: A cavity. Since the carious process is reversible before a cavity is present, it may be possible to arrest caries with fluoride and remineralize the tooth surface. When a cavity is present, a restoration will be needed to replace the lost tooth structure. At times, pit and fissure caries may be difficult to detect. Bacteria can penetrate the enamel to reach dentin, but then the outer surface may remineralize, especially if fluoride
792-457: A child from a caretaker's kiss or through feeding pre-masticated food. Bacteria in a person's mouth convert glucose, fructose, and most commonly sucrose (table sugar) into acids, mainly lactic acid, through a glycolytic process called fermentation. If left in contact with the tooth, these acids may cause demineralization, which is the dissolution of its mineral content. The process is dynamic, however, as remineralization can also occur if
924-552: A combination of sequence, structure and function, and they can be combined in many different ways. In an early study of 170,000 proteins, about two-thirds were assigned at least one domain, with larger proteins containing more domains (e.g. proteins larger than 600 amino acids having an average of more than 5 domains). Most proteins consist of linear polymers built from series of up to 20 different L -α- amino acids. All proteinogenic amino acids possess common structural features, including an α-carbon to which an amino group,
1056-402: A constriction of the tubules, which is an attempt to slow the bacterial progression. In addition, as the acid from the bacteria demineralizes the hydroxyapatite crystals, calcium and phosphorus are released, allowing for the precipitation of more crystals which fall deeper into the dentinal tubule. These crystals form a barrier and slow the advancement of caries. After these protective responses,
1188-403: A defined conformation . Proteins can interact with many types of molecules, including with other proteins , with lipids , with carbohydrates , and with DNA . It has been estimated that average-sized bacteria contain about 2 million proteins per cell (e.g. E. coli and Staphylococcus aureus ). Smaller bacteria, such as Mycoplasma or spirochetes contain fewer molecules, on
1320-834: A detailed review of the vegetable proteins at the Connecticut Agricultural Experiment Station . Then, working with Lafayette Mendel and applying Liebig's law of the minimum , which states that growth is limited by the scarcest resource, to the feeding of laboratory rats, the nutritionally essential amino acids were established. The work was continued and communicated by William Cumming Rose . The difficulty in purifying proteins in large quantities made them very difficult for early protein biochemists to study. Hence, early studies focused on proteins that could be purified in large quantities, including those of blood, egg whites, and various toxins, as well as digestive and metabolic enzymes obtained from slaughterhouses. In
1452-437: A few specific species of bacteria are believed to cause dental caries: Streptococcus mutans and Lactobacillus species among them. Streptococcus mutans are gram-positive bacteria which constitute biofilms on the surface of teeth. These organisms can produce high levels of lactic acid following fermentation of dietary sugars and are resistant to the adverse effects of low pH, properties essential for cariogenic bacteria. As
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#17331046584611584-452: A greater risk for cavities. Molar incisor hypo-mineralization seems to be increasingly common. While the cause is unknown it is thought to be a combination of genetic and environmental factors. Possible contributing factors that have been investigated include systemic factors such as high levels of dioxins or polychlorinated biphenyl (PCB) in the mother's milk, premature birth and oxygen deprivation at birth, and certain disorders during
1716-478: A little ambiguous and can overlap in meaning. Protein is generally used to refer to the complete biological molecule in a stable conformation , whereas peptide is generally reserved for a short amino acid oligomers often lacking a stable 3D structure. But the boundary between the two is not well defined and usually lies near 20–30 residues. Polypeptide can refer to any single linear chain of amino acids, usually regardless of length, but often implies an absence of
1848-399: A low rate of salivary flow (molar fissures). Grooves on the occlusal surfaces of molar and premolar teeth provide microscopic retention sites for plaque bacteria, as do the interproximal sites. Plaque may also collect above or below the gingiva , where it is referred to as supra- or sub-gingival plaque, respectively. These bacterial strains, most notably S. mutans , can be inherited by
1980-419: A mother's dental caries may decrease the risk in her children by decreasing the number of certain bacteria she may spread to them. Screening can result in earlier detection. Depending on the extent of destruction, various treatments can be used to restore the tooth to proper function, or the tooth may be removed . There is no known method to grow back large amounts of tooth. The availability of treatment
2112-410: A pH of 5.5. Dentin and cementum are more susceptible to caries than enamel because they have lower mineral content. Thus, when root surfaces of teeth are exposed from gingival recession or periodontal disease, caries can develop more readily. Even in a healthy oral environment, however, the tooth is susceptible to dental caries. The evidence for linking malocclusion and/or crowding to dental caries
2244-410: A particular cell or cell type is known as its proteome . The chief characteristic of proteins that also allows their diverse set of functions is their ability to bind other molecules specifically and tightly. The region of the protein responsible for binding another molecule is known as the binding site and is often a depression or "pocket" on the molecular surface. This binding ability is mediated by
2376-500: A protein carries out its function: for example, enzyme kinetics studies explore the chemical mechanism of an enzyme's catalytic activity and its relative affinity for various possible substrate molecules. By contrast, in vivo experiments can provide information about the physiological role of a protein in the context of a cell or even a whole organism . In silico studies use computational methods to study proteins. Proteins may be purified from other cellular components using
2508-411: A protein is defined by the sequence of a gene, which is encoded in the genetic code . In general, the genetic code specifies 20 standard amino acids; but in certain organisms the genetic code can include selenocysteine and—in certain archaea — pyrrolysine . Shortly after or even during synthesis, the residues in a protein are often chemically modified by post-translational modification , which alters
2640-539: A protein that fold into distinct structural units. Domains usually also have specific functions, such as enzymatic activities (e.g. kinase ) or they serve as binding modules (e.g. the SH3 domain binds to proline-rich sequences in other proteins). Short amino acid sequences within proteins often act as recognition sites for other proteins. For instance, SH3 domains typically bind to short PxxP motifs (i.e. 2 prolines [P], separated by two unspecified amino acids [x], although
2772-486: A role in biological recognition phenomena involving cells and proteins. Receptors and hormones are highly specific binding proteins. Transmembrane proteins can also serve as ligand transport proteins that alter the permeability of the cell membrane to small molecules and ions. The membrane alone has a hydrophobic core through which polar or charged molecules cannot diffuse . Membrane proteins contain internal channels that allow such molecules to enter and exit
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#17331046584612904-406: A series of purification steps may be necessary to obtain protein sufficiently pure for laboratory applications. To simplify this process, genetic engineering is often used to add chemical features to proteins that make them easier to purify without affecting their structure or activity. Here, a "tag" consisting of a specific amino acid sequence, often a series of histidine residues (a " His-tag "),
3036-432: A solution known as a crude lysate . The resulting mixture can be purified using ultracentrifugation , which fractionates the various cellular components into fractions containing soluble proteins; membrane lipids and proteins; cellular organelles , and nucleic acids . Precipitation by a method known as salting out can concentrate the proteins from this lysate. Various types of chromatography are then used to isolate
3168-451: A specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide . A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides . The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid residues in
3300-434: A tooth that is exposed to the oral cavity, but not the structures that are retained within the bone. Tooth decay is caused by biofilm (dental plaque) lying on the teeth and maturing to become cariogenic (causing decay). Certain bacteria in the biofilm produce acids, primarily lactic acid , in the presence of fermentable carbohydrates such as sucrose , fructose , and glucose . Caries occur more often in people from
3432-441: A variety of techniques such as ultracentrifugation , precipitation , electrophoresis , and chromatography ; the advent of genetic engineering has made possible a number of methods to facilitate purification. To perform in vitro analysis, a protein must be purified away from other cellular components. This process usually begins with cell lysis , in which a cell's membrane is disrupted and its internal contents released into
3564-432: A vast array of functions within organisms, including catalysing metabolic reactions , DNA replication , responding to stimuli , providing structure to cells and organisms , and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes , and which usually results in protein folding into
3696-413: A zone of demineralized dentin due to acid and has no bacteria present. The zones of bacterial penetration and destruction are the locations of invading bacteria and ultimately the decomposition of dentin. The zone of destruction has a more mixed bacterial population where proteolytic enzymes have destroyed the organic matrix. The innermost dentin caries has been reversibly attacked because the collagen matrix
3828-427: Is a chronic condition that forms a large, shallow lesion and slowly invades first the root's cementum and then dentin to cause a chronic infection of the pulp (see further discussion under classification by affected hard tissue). Because dental pain is a late finding, many lesions are not detected early, resulting in restorative challenges and increased tooth loss. The presentation of caries is highly variable. However,
3960-519: Is a disease in which the enamel does not fully form or forms in insufficient amounts and can fall off a tooth. In both cases, teeth may be left more vulnerable to decay because the enamel is not able to protect the tooth. In most people, disorders or diseases affecting teeth are not the primary cause of dental caries. Approximately 96% of tooth enamel is composed of minerals. These minerals, especially hydroxyapatite , will become soluble when exposed to acidic environments. Enamel begins to demineralize at
4092-405: Is a risk factor. If mineral breakdown is greater than buildup from sources such as saliva , caries results. Risk factors include conditions that result in less saliva, such as diabetes mellitus , Sjögren syndrome and some medications. Medications that decrease saliva production include antihistamines and antidepressants . Dental caries are also associated with poverty , poor cleaning of
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4224-412: Is a significant risk factor for periodontal disease, which can cause the gingiva to recede . As the gingiva loses attachment to the teeth due to gingival recession, the root surface becomes more visible in the mouth. If this occurs, root caries is a concern since the cementum covering the roots of teeth is more easily demineralized by acids than enamel. Currently, there is not enough evidence to support
4356-463: Is an ecologic shift within the dental biofilm from a balanced population of microorganisms to a population that produces acids and can survive in an acid environment. Tooth enamel is a highly mineralized acellular tissue, and caries act upon it through a chemical process brought on by the acidic environment produced by bacteria. As the bacteria consume the sugar and use it for their own energy, they produce lactic acid. The effects of this process include
4488-445: Is attached to one terminus of the protein. As a result, when the lysate is passed over a chromatography column containing nickel , the histidine residues ligate the nickel and attach to the column while the untagged components of the lysate pass unimpeded. A number of different tags have been developed to help researchers purify specific proteins from complex mixtures. Caries Tooth decay , also known as cavities or caries ,
4620-437: Is characterized by demineralization of the tooth surface, altering the tooth's optical properties. Technology using laser speckle image (LSI) techniques may provide a diagnostic aid to detect early carious lesions. Caries can be classified by location, etiology, rate of progression, and affected hard tissues. These forms of classification can be used to characterize a particular case of tooth decay to more accurately represent
4752-628: Is found in hard or filamentous structures such as hair , nails , feathers , hooves , and some animal shells . Some globular proteins can also play structural functions, for example, actin and tubulin are globular and soluble as monomers, but polymerize to form long, stiff fibers that make up the cytoskeleton , which allows the cell to maintain its shape and size. Other proteins that serve structural functions are motor proteins such as myosin , kinesin , and dynein , which are capable of generating mechanical forces. These proteins are crucial for cellular motility of single celled organisms and
4884-469: Is higher in prokaryotes than eukaryotes and can reach up to 20 amino acids per second. The process of synthesizing a protein from an mRNA template is known as translation . The mRNA is loaded onto the ribosome and is read three nucleotides at a time by matching each codon to its base pairing anticodon located on a transfer RNA molecule, which carries the amino acid corresponding to the codon it recognizes. The enzyme aminoacyl tRNA synthetase "charges"
5016-453: Is in fact more cariogenic than a mixture of equal parts of glucose and fructose. This is due to the bacteria using the energy in the saccharide bond between the glucose and fructose subunits. S.mutans adheres to the biofilm on the tooth by converting sucrose into an extremely adhesive substance called dextran polysaccharide by the enzyme dextran sucranase. The frequency with which teeth are exposed to cariogenic (acidic) environments affects
5148-461: Is inefficient for polypeptides longer than about 300 amino acids, and the synthesized proteins may not readily assume their native tertiary structure . Most chemical synthesis methods proceed from C-terminus to N-terminus, opposite the biological reaction. Most proteins fold into unique 3D structures. The shape into which a protein naturally folds is known as its native conformation . Although many proteins can fold unassisted, simply through
5280-559: Is not present to counterbalance the acidic environment created by certain foods. As a result, medical conditions that reduce the amount of saliva produced by salivary glands , in particular the submandibular gland and parotid gland , are likely to lead to dry mouth and thus to widespread tooth decay. Examples include Sjögren syndrome , diabetes mellitus , diabetes insipidus , and sarcoidosis . Medications, such as antihistamines and antidepressants, can also impair salivary flow. Stimulants, most notoriously methylamphetamine , also occlude
5412-432: Is not severely damaged, giving it potential for repair. The structure of dentin is an arrangement of microscopic channels, called dentinal tubules , which radiate outward from the pulp chamber to the exterior cementum or enamel border. The diameter of the dentinal tubules is largest near the pulp (about 2.5 μm) and smallest (about 900 nm) at the junction of dentin and enamel. The carious process continues through
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5544-418: Is often diagnosed by blowing air across the suspect surface, which removes moisture and changes the optical properties of the unmineralized enamel. Some dental researchers have cautioned against the use of dental explorers to find caries, in particular sharp ended explorers. In cases where a small area of tooth has begun demineralizing but has not yet cavitated, the pressure from the dental explorer could cause
5676-404: Is often enormous—as much as 10 -fold increase in rate over the uncatalysed reaction in the case of orotate decarboxylase (78 million years without the enzyme, 18 milliseconds with the enzyme). The molecules bound and acted upon by enzymes are called substrates . Although enzymes can consist of hundreds of amino acids, it is usually only a small fraction of the residues that come in contact with
5808-416: Is often poor in the developing world. Paracetamol (acetaminophen) or ibuprofen may be taken for pain. Worldwide, approximately 3.6 billion people (48% of the population) have dental caries in their permanent teeth as of 2016. The World Health Organization estimates that nearly all adults have dental caries at some point in time. In baby teeth it affects about 620 million people or 9% of
5940-425: Is present until the loss of tooth structure results in a cavitation. Unlike enamel, the dentin reacts to the progression of dental caries. After tooth formation , the ameloblasts , which produce enamel, are destroyed once enamel formation is complete and thus cannot later regenerate enamel after its destruction. On the other hand, dentin is produced continuously throughout life by odontoblasts , which reside at
6072-419: Is present. These caries, sometimes referred to as "hidden caries", will still be visible on X-ray radiographs, but visual examination of the tooth would show the enamel intact or minimally perforated. The differential diagnosis for dental caries includes dental fluorosis and developmental defects of the tooth including hypomineralization of the tooth and hypoplasia of the tooth. The early carious lesion
6204-438: Is still unknown if the identification of high-risk individuals can lead to more effective long-term patient management that prevents caries initiation and arrests or reverses the progression of lesions. Saliva also contains iodine and EGF . EGF results effective in cellular proliferation, differentiation and survival. Salivary EGF, which seems also regulated by dietary inorganic iodine, plays an important physiological role in
6336-420: Is the breakdown of teeth due to acids produced by bacteria . The cavities may be a number of different colors, from yellow to black. Symptoms may include pain and difficulty eating. Complications may include inflammation of the tissue around the tooth , tooth loss and infection or abscess formation. Tooth regeneration is an ongoing stem cell–based field of study that aims to find methods to reverse
6468-532: Is the code for methionine . Because DNA contains four nucleotides, the total number of possible codons is 64; hence, there is some redundancy in the genetic code, with some amino acids specified by more than one codon. Genes encoded in DNA are first transcribed into pre- messenger RNA (mRNA) by proteins such as RNA polymerase . Most organisms then process the pre-mRNA (also known as a primary transcript ) using various forms of post-transcriptional modification to form
6600-413: Is the first visible sign of caries and coincides with a one to two percent loss of minerals. A slight remineralization of enamel occurs in the dark zone, which serves as an example of how the development of dental caries is an active process with alternating changes. The area of greatest demineralization and destruction is in the body of the lesion itself. The surface zone remains relatively mineralized and
6732-418: Is weak; however, the anatomy of teeth may affect the likelihood of caries formation. Where the deep developmental grooves of teeth are more numerous and exaggerated, pit and fissure caries is more likely to develop (see next section). Also, caries is more likely to develop when food is trapped between teeth. Reduced salivary flow rate is associated with increased caries since the buffering capability of saliva
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#17331046584616864-486: The amino acid leucine for which he found a (nearly correct) molecular weight of 131 Da . Early nutritional scientists such as the German Carl von Voit believed that protein was the most important nutrient for maintaining the structure of the body, because it was generally believed that "flesh makes flesh." Around 1862, Karl Heinrich Ritthausen isolated the amino acid glutamic acid . Thomas Burr Osborne compiled
6996-527: The cells in salivary glands, somewhat increasing the likelihood of caries formation. Susceptibility to caries can be related to altered metabolism in the tooth, in particular to fluid flow in the dentin. Experiments on rats have shown that a high-sucrose, cariogenic diet "significantly suppresses the rate of fluid motion" in dentin. The use of tobacco may also increase the risk for caries formation. Some brands of smokeless tobacco contain high sugar content, increasing susceptibility to caries. Tobacco use
7128-443: The cementum of root surfaces is more easily demineralized than enamel surfaces, a wider variety of bacteria can cause root caries, including Lactobacillus acidophilus , Actinomyces spp. , Nocardia spp. , and Streptococcus mutans . Bacteria collect around the teeth and gums in a sticky, creamy-coloured mass called plaque , which serves as a biofilm . Some sites collect plaque more commonly than others, for example, sites with
7260-461: The dental plaque . However, these four criteria are not always enough to cause the disease and a sheltered environment promoting development of a cariogenic biofilm is required. The caries disease process does not have an inevitable outcome, and different individuals will be susceptible to different degrees depending on the shape of their teeth, oral hygiene habits, and the buffering capacity of their saliva. Dental caries can occur on any surface of
7392-644: The muscle sarcomere , with a molecular mass of almost 3,000 kDa and a total length of almost 27,000 amino acids. Short proteins can also be synthesized chemically by a family of methods known as peptide synthesis , which rely on organic synthesis techniques such as chemical ligation to produce peptides in high yield. Chemical synthesis allows for the introduction of non-natural amino acids into polypeptide chains, such as attachment of fluorescent probes to amino acid side chains. These methods are useful in laboratory biochemistry and cell biology , though generally not for commercial applications. Chemical synthesis
7524-645: The sperm of many multicellular organisms which reproduce sexually . They also generate the forces exerted by contracting muscles and play essential roles in intracellular transport. A key question in molecular biology is how proteins evolve, i.e. how can mutations (or rather changes in amino acid sequence) lead to new structures and functions? Most amino acids in a protein can be changed without disrupting activity or function, as can be seen from numerous homologous proteins across species (as collected in specialized databases for protein families , e.g. PFAM ). In order to prevent dramatic consequences of mutations,
7656-493: The 1700s by Antoine Fourcroy and others, who often collectively called them " albumins ", or "albuminous materials" ( Eiweisskörper , in German). Gluten , for example, was first separated from wheat in published research around 1747, and later determined to exist in many plants. In 1789, Antoine Fourcroy recognized three distinct varieties of animal proteins: albumin , fibrin , and gelatin . Vegetable (plant) proteins studied in
7788-562: The 1950s, the Armour Hot Dog Company purified 1 kg of pure bovine pancreatic ribonuclease A and made it freely available to scientists; this gesture helped ribonuclease A become a major target for biochemical study for the following decades. The understanding of proteins as polypeptides , or chains of amino acids, came through the work of Franz Hofmeister and Hermann Emil Fischer in 1902. The central role of proteins as enzymes in living organisms that catalyzed reactions
7920-498: The 20,000 or so proteins encoded by the human genome, only 6,000 are detected in lymphoblastoid cells. Proteins are assembled from amino acids using information encoded in genes. Each protein has its own unique amino acid sequence that is specified by the nucleotide sequence of the gene encoding this protein. The genetic code is a set of three-nucleotide sets called codons and each three-nucleotide combination designates an amino acid, for example AUG ( adenine – uracil – guanine )
8052-516: The EC number system provides a functional classification scheme. Similarly, the gene ontology classifies both genes and proteins by their biological and biochemical function, but also by their intracellular location. Sequence similarity is used to classify proteins both in terms of evolutionary and functional similarity. This may use either whole proteins or protein domains , especially in multi-domain proteins . Protein domains allow protein classification by
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#17331046584618184-765: The Wnt signaling cascade is only one aspect of their mode of action. The conserved homology domain HD1 of BCL9 (and BCL9L) has recently been shown to be interacting with TBX3 in the context of intestinal carcinogenesis; this interaction mediates some tissue-specific signalling functions of the protein. BCL9 is associated with B-cell acute lymphoblastic leukemia . It may be a target of translocation in B-cell malignancies with abnormalities of 1q21. The overexpression of BCL9 may be of pathogenic significance in B-cell malignancies. BCL9 and BCL9L are potential clinical targets for human cancers; for instance,
8316-709: The ability of many enzymes to bind and process multiple substrates . When mutations occur, the specificity of an enzyme can increase (or decrease) and thus its enzymatic activity. Thus, bacteria (or other organisms) can adapt to different food sources, including unnatural substrates such as plastic. Methods commonly used to study protein structure and function include immunohistochemistry , site-directed mutagenesis , X-ray crystallography , nuclear magnetic resonance and mass spectrometry . The activities and structures of proteins may be examined in vitro , in vivo , and in silico . In vitro studies of purified proteins in controlled environments are useful for learning how
8448-420: The acid is neutralized by saliva or mouthwash . Fluoride toothpaste or dental varnish may aid remineralization. If demineralization continues over time, enough mineral content may be lost so that the soft organic material left behind disintegrates, forming a cavity or hole. The impact such sugars have on the progress of dental caries is called cariogenicity. Sucrose, although a bound glucose and fructose unit,
8580-405: The addition of a single methyl group to a binding partner can sometimes suffice to nearly eliminate binding; for example, the aminoacyl tRNA synthetase specific to the amino acid valine discriminates against the very similar side chain of the amino acid isoleucine . Proteins can bind to other proteins as well as to small-molecule substrates. When proteins bind specifically to other copies of
8712-595: The alpha carbons are roughly coplanar . The other two dihedral angles in the peptide bond determine the local shape assumed by the protein backbone. The end with a free amino group is known as the N-terminus or amino terminus, whereas the end of the protein with a free carboxyl group is known as the C-terminus or carboxy terminus (the sequence of the protein is written from N-terminus to C-terminus, from left to right). The words protein , polypeptide, and peptide are
8844-531: The amino acid side chains in a protein that ultimately determines its three-dimensional structure and its chemical reactivity. The amino acids in a polypeptide chain are linked by peptide bonds . Once linked in the protein chain, an individual amino acid is called a residue, and the linked series of carbon, nitrogen, and oxygen atoms are known as the main chain or protein backbone. The peptide bond has two resonance forms that contribute some double-bond character and inhibit rotation around its axis, so that
8976-574: The binding of a substrate molecule to an enzyme's active site , or the physical region of the protein that participates in chemical catalysis. In solution, proteins also undergo variation in structure through thermal vibration and the collision with other molecules. Proteins can be informally divided into three main classes, which correlate with typical tertiary structures: globular proteins , fibrous proteins , and membrane proteins . Almost all globular proteins are soluble and many are enzymes. Fibrous proteins are often structural, such as collagen ,
9108-570: The body of a multicellular organism. These proteins must have a high binding affinity when their ligand is present in high concentrations, but must also release the ligand when it is present at low concentrations in the target tissues. The canonical example of a ligand-binding protein is haemoglobin , which transports oxygen from the lungs to other organs and tissues in all vertebrates and has close homologs in every biological kingdom . Lectins are sugar-binding proteins which are highly specific for their sugar moieties. Lectins typically play
9240-425: The border between the pulp and dentin. Since odontoblasts are present, a stimulus, such as caries, can trigger a biologic response. These defense mechanisms include the formation of sclerotic and tertiary dentin . In dentin from the deepest layer to the enamel, the distinct areas affected by caries are the advancing front, the zone of bacterial penetration, and the zone of destruction. The advancing front represents
9372-423: The calcium ion and therefore exposure to them may promote tooth decay. Poverty is also a significant social determinant for oral health. Dental caries have been linked with lower socio-economic status and can be considered a disease of poverty. Forms are available for risk assessment for caries when treating dental cases; this system using the evidence-based Caries Management by Risk Assessment (CAMBRA). It
9504-558: The cell is as enzymes , which catalyse chemical reactions. Enzymes are usually highly specific and accelerate only one or a few chemical reactions. Enzymes carry out most of the reactions involved in metabolism , as well as manipulating DNA in processes such as DNA replication , DNA repair , and transcription . Some enzymes act on other proteins to add or remove chemical groups in a process known as posttranslational modification. About 4,000 reactions are known to be catalysed by enzymes. The rate acceleration conferred by enzymatic catalysis
9636-436: The cell surface and an effector domain within the cell, which may have enzymatic activity or may undergo a conformational change detected by other proteins within the cell. Antibodies are protein components of an adaptive immune system whose main function is to bind antigens , or foreign substances in the body, and target them for destruction. Antibodies can be secreted into the extracellular environment or anchored in
9768-752: The cell's machinery through the process of protein turnover . A protein's lifespan is measured in terms of its half-life and covers a wide range. They can exist for minutes or years with an average lifespan of 1–2 days in mammalian cells. Abnormal or misfolded proteins are degraded more rapidly either due to being targeted for destruction or due to being unstable. Like other biological macromolecules such as polysaccharides and nucleic acids , proteins are essential parts of organisms and participate in virtually every process within cells . Many proteins are enzymes that catalyse biochemical reactions and are vital to metabolism . Proteins also have structural or mechanical functions, such as actin and myosin in muscle and
9900-450: The cell. Many ion channel proteins are specialized to select for only a particular ion; for example, potassium and sodium channels often discriminate for only one of the two ions. Structural proteins confer stiffness and rigidity to otherwise-fluid biological components. Most structural proteins are fibrous proteins ; for example, collagen and elastin are critical components of connective tissue such as cartilage , and keratin
10032-667: The cementum enveloping the root surface is not nearly as durable as the enamel encasing the crown , root caries tend to progress much more rapidly than decay on other surfaces. The progression and loss of mineralization on the root surface is 2.5 times faster than caries in enamel. In very severe cases where oral hygiene is very poor and where the diet is very rich in fermentable carbohydrates, caries may cause cavities within months of tooth eruption. This can occur, for example, when children continuously drink sugary drinks from baby bottles (see later discussion). There are certain diseases and disorders affecting teeth that may leave an individual at
10164-621: The chemical properties of their amino acids, others require the aid of molecular chaperones to fold into their native states. Biochemists often refer to four distinct aspects of a protein's structure: Proteins are not entirely rigid molecules. In addition to these levels of structure, proteins may shift between several related structures while they perform their functions. In the context of these functional rearrangements, these tertiary or quaternary structures are usually referred to as " conformations ", and transitions between them are called conformational changes. Such changes are often induced by
10296-441: The chief actors within the cell, said to be carrying out the duties specified by the information encoded in genes. With the exception of certain types of RNA , most other biological molecules are relatively inert elements upon which proteins act. Proteins make up half the dry weight of an Escherichia coli cell, whereas other macromolecules such as DNA and RNA make up only 3% and 20%, respectively. The set of proteins expressed in
10428-408: The child's first 3 years such as mumps , diphtheria , scarlet fever , measles , hypoparathyroidism , malnutrition , malabsorption , hypo-vitaminosis D , chronic respiratory diseases , or undiagnosed and untreated coeliac disease , which usually presents with mild or absent gastrointestinal symptoms. Amelogenesis imperfecta , which occurs in between 1 in 718 and 1 in 14,000 individuals,
10560-422: The condition to others and also indicate the severity of tooth destruction. In some instances, caries is described in other ways that might indicate the cause. The G. V. Black classification is as follows: Early childhood caries (ECC), also known as " baby bottle caries ," " baby bottle tooth decay" or "bottle rot," is a pattern of decay found in young children with their deciduous (baby) teeth. This must include
10692-490: The construction of enormously complex signaling networks. As interactions between proteins are reversible, and depend heavily on the availability of different groups of partner proteins to form aggregates that are capable to carry out discrete sets of function, study of the interactions between specific proteins is a key to understand important aspects of cellular function, and ultimately the properties that distinguish particular cell types. The best-known role of proteins in
10824-456: The cytoplasm of ameloblasts, the cells that secrete enamel proteins, and colocalize in these cells with amelogenin, the main component of enamel, encoded by the AMELX gene, which has been already implicated as a causative factor of Amelogenesis Imperfecta in humans. Bcl9 interacts with amelogenin and proteins involved in exocytosis and vesicular trafficking, suggesting that these proteins function in
10956-444: The day. Another pattern of decay is "rampant caries", which signifies advanced or severe decay on multiple surfaces of many teeth. Rampant caries may be seen in individuals with xerostomia , poor oral hygiene, stimulant use (due to drug-induced dry mouth ), and/or large sugar intake. If rampant caries is a result of previous radiation to the head and neck, it may be described as radiation-induced caries. Problems can also be caused by
11088-448: The decay has progressed enough to allow the bacteria to overwhelm the pulp tissue in the center of the tooth, a toothache can result, and the pain will become more constant. Death of the pulp tissue and infection are common consequences. The tooth will no longer be sensitive to hot or cold but can be very tender to pressure. Dental caries can also cause bad breath and foul tastes. In highly progressed cases, an infection can spread from
11220-436: The demineralization of crystals in the enamel, caused by acids, over time until the bacteria physically penetrate the dentin. Enamel rods , which are the basic unit of the enamel structure, run perpendicularly from the surface of the tooth to the dentin. Since demineralization of enamel by caries follows the direction of the enamel rods, the different triangular patterns between pit and fissure and smooth-surface caries develop in
11352-635: The demineralization process has stopped, leaving a stain. Active decay is lighter in color and dull in appearance. As the enamel and dentin are destroyed, the cavity becomes more noticeable. The affected areas of the tooth change color and become soft to the touch. Once the decay passes through the enamel, the dentinal tubules , which have passages to the nerve of the tooth, become exposed, resulting in pain that can be transient, temporarily worsening with exposure to heat, cold, or sweet foods and drinks. A tooth weakened by extensive internal decay can sometimes suddenly fracture under normal chewing forces. When
11484-410: The dental caries, then the dentin produced is called "reactionary" dentin. If the odontoblasts are killed, the dentin produced is called "reparative" dentin. In the case of reparative dentin, other cells are needed to assume the role of the destroyed odontoblasts. Growth factors , especially TGF-β , are thought to initiate the production of reparative dentin by fibroblasts and mesenchymal cells of
11616-440: The dentin is considered sclerotic. According to hydrodynamic theory , fluids within dentinal tubules are believed to be the mechanism by which pain receptors are triggered within the pulp of the tooth. Since sclerotic dentin prevents the passage of such fluids, pain that would otherwise serve as a warning of the invading bacteria may not develop at first. In response to dental caries, there may be production of more dentin toward
11748-413: The dentinal tubules, which are responsible for the triangular patterns resulting from the progression of caries deep into the tooth. The tubules also allow caries to progress faster. In response, the fluid inside the tubules brings immunoglobulins from the immune system to fight the bacterial infection. At the same time, there is an increase of mineralization of the surrounding tubules. This results in
11880-408: The derivative unit kilodalton (kDa). The average size of a protein increases from Archaea to Bacteria to Eukaryote (283, 311, 438 residues and 31, 34, 49 kDa respectively) due to a bigger number of protein domains constituting proteins in higher organisms. For instance, yeast proteins are on average 466 amino acids long and 53 kDa in mass. The largest known proteins are the titins , a component of
12012-408: The development of dental caries relies heavily on the frequency of acid exposure. The carious process can begin within days of a tooth's erupting into the mouth if the diet is sufficiently rich in suitable carbohydrates. Evidence suggests that the introduction of fluoride treatments has slowed the process. Proximal caries take an average of four years to pass through enamel in permanent teeth. Because
12144-408: The direction of the pulp. This new dentin is referred to as tertiary dentin. Tertiary dentin is produced to protect the pulp for as long as possible from the advancing bacteria. As more tertiary dentin is produced, the size of the pulp decreases. This type of dentin has been subdivided according to the presence or absence of the original odontoblasts. If the odontoblasts survive long enough to react to
12276-419: The disease) are present in dental plaque, but they are usually in too low concentrations to cause problems unless there is a shift in the balance. This is driven by local environmental change, such as frequent sugar intake or inadequate biofilm removal (toothbrushing). If left untreated, the disease can lead to pain, tooth loss and infection . The mouth contains a wide variety of oral bacteria , but only
12408-402: The effects of decay; current methods are based on easing symptoms. The cause of cavities is acid from bacteria dissolving the hard tissues of the teeth ( enamel , dentin and cementum ). The acid is produced by the bacteria when they break down food debris or sugar on the tooth surface. Simple sugars in food are these bacteria's primary energy source and thus a diet high in simple sugar
12540-416: The enamel because the orientation of enamel rods are different in the two areas of the tooth. As the enamel loses minerals, and dental caries progresses, the enamel develops several distinct zones, visible under a light microscope. From the deepest layer of the enamel to the enamel surface, the identified areas are the: translucent zone, dark zones, body of the lesion, and surface zone. The translucent zone
12672-447: The erroneous conclusion that they might be composed of a single type of (very large) molecule. The term "protein" to describe these molecules was proposed by Mulder's associate Berzelius; protein is derived from the Greek word πρώτειος ( proteios ), meaning "primary", "in the lead", or "standing in front", + -in . Mulder went on to identify the products of protein degradation such as
12804-476: The flow of saliva to an extreme degree. This is known as meth mouth . Tetrahydrocannabinol (THC), the active chemical substance in cannabis , also causes a nearly complete occlusion of salivation, known in colloquial terms as "cotton mouth". Moreover, 63% of the most commonly prescribed medications in the United States list dry mouth as a known side-effect. Radiation therapy of the head and neck may also damage
12936-455: The gene expression changes that they promote is associated with a poor outcome in colorectal cancer . Like BCL2 , BCL3 , BCL5, BCL6 , BCL7A, and BCL10 , it has clinical significance in lymphoma . Common variations in the BCL9 gene, which is in the distal area, confer risk of schizophrenia and may also be associated with bipolar disorder and major depressive disorder . BCL9, together with
13068-525: The late 1700s and early 1800s included gluten , plant albumin , gliadin , and legumin . Proteins were first described by the Dutch chemist Gerardus Johannes Mulder and named by the Swedish chemist Jöns Jacob Berzelius in 1838. Mulder carried out elemental analysis of common proteins and found that nearly all proteins had the same empirical formula , C 400 H 620 N 100 O 120 P 1 S 1 . He came to
13200-523: The likelihood of caries development. After meals or snacks , the bacteria in the mouth metabolize sugar, resulting in an acidic by-product that decreases pH. As time progresses, the pH returns to normal due to the buffering capacity of saliva and the dissolved mineral content of tooth surfaces. During every exposure to the acidic environment, portions of the inorganic mineral content at the surface of teeth dissolve and can remain dissolved for two hours. Since teeth are vulnerable during these acidic periods,
13332-453: The lower end of the socio-economic scale than people from the upper end of the socio-economic scale, due to lack of education about dental care, and lack of access to professional dental care which may be expensive. The most common bacteria associated with dental cavities are the mutans streptococci, most prominently Streptococcus mutans and Streptococcus sobrinus , and lactobacilli . However, cariogenic bacteria (the ones that can cause
13464-413: The maintenance of oral (and gastro-oesophageal) tissue integrity, and, on the other hand, iodine is effective in prevention of dental caries and oral health. Teeth are bathed in saliva and have a coating of bacteria on them ( biofilm ) that continually forms. The development of biofilm begins with pellicle formation. Pellicle is an acellular proteinaceous film which covers the teeth. Bacteria colonize on
13596-478: The major component of connective tissue, or keratin , the protein component of hair and nails. Membrane proteins often serve as receptors or provide channels for polar or charged molecules to pass through the cell membrane . A special case of intramolecular hydrogen bonds within proteins, poorly shielded from water attack and hence promoting their own dehydration , are called dehydrons . Many proteins are composed of several protein domains , i.e. segments of
13728-443: The mature mRNA, which is then used as a template for protein synthesis by the ribosome . In prokaryotes the mRNA may either be used as soon as it is produced, or be bound by a ribosome after having moved away from the nucleoid . In contrast, eukaryotes make mRNA in the cell nucleus and then translocate it across the nuclear membrane into the cytoplasm , where protein synthesis then takes place. The rate of protein synthesis
13860-405: The membranes of specialized B cells known as plasma cells . Whereas enzymes are limited in their binding affinity for their substrates by the necessity of conducting their reaction, antibodies have no such constraints. An antibody's binding affinity to its target is extraordinarily high. Many ligand transport proteins bind particular small biomolecules and transport them to other locations in
13992-401: The mouth , and receding gums resulting in exposure of the roots of the teeth. Prevention of dental caries includes regular cleaning of the teeth, a diet low in sugar, and small amounts of fluoride . Brushing one's teeth twice per day, and flossing between the teeth once a day is recommended. Fluoride may be acquired from water , salt or toothpaste among other sources. Treating
14124-496: The nobel prize in 1972, solidified the thermodynamic hypothesis of protein folding, according to which the folded form of a protein represents its free energy minimum. With the development of X-ray crystallography , it became possible to determine protein structures as well as their sequences. The first protein structures to be solved were hemoglobin by Max Perutz and myoglobin by John Kendrew , in 1958. The use of computers and increasing computing power also supported
14256-500: The order of 50,000 to 1 million. By contrast, eukaryotic cells are larger and thus contain much more protein. For instance, yeast cells have been estimated to contain about 50 million proteins and human cells on the order of 1 to 3 billion. The concentration of individual protein copies ranges from a few molecules per cell up to 20 million. Not all genes coding proteins are expressed in most cells and their number depends on, for example, cell type and external stimuli. For instance, of
14388-476: The paralogue protein BCL9l and PYGO2 also have cytoplasmic functions during tooth development and is particularly important for the formation of enamel. Mice lacking both Pygo1 and Pygo2 or both Bcl9 and Bcl9l develop teeth, a process that requires Wnt/β-catenin transcriptional regulation, but the enamel is structurally disorganized and contains less iron than teeth from control mice. Bcl9, Bcl9l, and Pygo2 are present in
14520-440: The physical and chemical properties, folding, stability, activity, and ultimately, the function of the proteins. Some proteins have non-peptide groups attached, which can be called prosthetic groups or cofactors . Proteins can also work together to achieve a particular function, and they often associate to form stable protein complexes . Once formed, proteins only exist for a certain period and are then degraded and recycled by
14652-414: The population. They have become more common in both children and adults in recent years. The disease is most common in the developed world due to greater simple sugar consumption, but less common in the developing world. Caries is Latin for "rottenness". A person experiencing caries may not be aware of the disease. The earliest sign of a new carious lesion is the appearance of a chalky white spot on
14784-421: The presence of at least one carious lesion on a primary tooth in a child under the age of 6 years. The teeth most likely affected are the maxillary anterior teeth, but all teeth can be affected. The name for this type of caries comes from the fact that the decay usually is a result of allowing children to fall asleep with sweetened liquids in their bottles or feeding children sweetened liquids multiple times during
14916-424: The process of cell signaling and signal transduction . Some proteins, such as insulin , are extracellular proteins that transmit a signal from the cell in which they were synthesized to other cells in distant tissues . Others are membrane proteins that act as receptors whose main function is to bind a signaling molecule and induce a biochemical response in the cell. Many receptors have a binding site exposed on
15048-534: The protein or proteins of interest based on properties such as molecular weight, net charge and binding affinity. The level of purification can be monitored using various types of gel electrophoresis if the desired protein's molecular weight and isoelectric point are known, by spectroscopy if the protein has distinguishable spectroscopic features, or by enzyme assays if the protein has enzymatic activity. Additionally, proteins can be isolated according to their charge using electrofocusing . For natural proteins,
15180-427: The proteins in the cytoskeleton , which form a system of scaffolding that maintains cell shape. Other proteins are important in cell signaling, immune responses , cell adhesion , and the cell cycle . In animals, proteins are needed in the diet to provide the essential amino acids that cannot be synthesized . Digestion breaks the proteins down for metabolic use. Proteins have been studied and recognized since
15312-457: The pulp. Reparative dentin is produced at an average of 1.5 μm/day, but can be increased to 3.5 μm/day. The resulting dentin contains irregularly shaped dentinal tubules that may not line up with existing dentinal tubules. This diminishes the ability for dental caries to progress within the dentinal tubules. The incidence of cemental caries increases in older adults as gingival recession occurs from either trauma or periodontal disease. It
15444-491: The risk factors and stages of development are similar. Initially, it may appear as a small chalky area (smooth surface caries), which may eventually develop into a large cavitation. Sometimes caries may be directly visible. However other methods of detection such as X-rays are used for less visible areas of teeth and to judge the extent of destruction. Lasers for detecting caries allow detection without ionizing radiation and are now used for detection of interproximal decay (between
15576-582: The same molecule, they can oligomerize to form fibrils; this process occurs often in structural proteins that consist of globular monomers that self-associate to form rigid fibers. Protein–protein interactions also regulate enzymatic activity, control progression through the cell cycle , and allow the assembly of large protein complexes that carry out many closely related reactions with a common biological function. Proteins can also bind to, or even be integrated into, cell membranes. The ability of binding partners to induce conformational changes in proteins allows
15708-573: The sample, allowing scientists to obtain more information and analyze larger structures. Computational protein structure prediction of small protein structural domains has also helped researchers to approach atomic-level resolution of protein structures. As of April 2024 , the Protein Data Bank contains 181,018 X-ray, 19,809 EM and 12,697 NMR protein structures. Proteins are primarily classified by sequence and structure, although other classifications are commonly used. Especially for enzymes
15840-430: The sequencing of complex proteins. In 1999, Roger Kornberg succeeded in sequencing the highly complex structure of RNA polymerase using high intensity X-rays from synchrotrons . Since then, cryo-electron microscopy (cryo-EM) of large macromolecular assemblies has been developed. Cryo-EM uses protein samples that are frozen rather than crystals, and beams of electrons rather than X-rays. It causes less damage to
15972-405: The substrate, and an even smaller fraction—three to four residues on average—that are directly involved in catalysis. The region of the enzyme that binds the substrate and contains the catalytic residues is known as the active site . Dirigent proteins are members of a class of proteins that dictate the stereochemistry of a compound synthesized by other enzymes. Many proteins are involved in
16104-508: The surface of the tooth, indicating an area of demineralization of enamel . This is referred to as a white spot lesion, an incipient carious lesion, or a "micro-cavity". As the lesion continues to demineralize, it can turn brown but will eventually turn into a cavitation ("cavity"). Before the cavity forms, the process is reversible, but once a cavity forms, the lost tooth structure cannot be regenerated . A lesion that appears dark brown and shiny suggests dental caries were once present, but
16236-706: The surrounding amino acids may determine the exact binding specificity). Many such motifs has been collected in the Eukaryotic Linear Motif (ELM) database. Topology of a protein describes the entanglement of the backbone and the arrangement of contacts within the folded chain. Two theoretical frameworks of knot theory and Circuit topology have been applied to characterise protein topology. Being able to describe protein topology opens up new pathways for protein engineering and pharmaceutical development, and adds to our understanding of protein misfolding diseases such as neuromuscular disorders and cancer. Proteins are
16368-400: The tRNA molecules with the correct amino acids. The growing polypeptide is often termed the nascent chain . Proteins are always biosynthesized from N-terminus to C-terminus . The size of a synthesized protein can be measured by the number of amino acids it contains and by its total molecular mass , which is normally reported in units of daltons (synonymous with atomic mass units ), or
16500-434: The teeth by adhering to the pellicle-coated surface. Over time, a mature biofilm is formed, creating a cariogenic environment on the tooth surface. The minerals in the hard tissues of the teeth – enamel, dentin and cementum – are constantly undergoing demineralization and remineralization. Dental caries result when the demineralization rate is faster than the remineralization, producing net mineral loss, which occurs when there
16632-557: The teeth). Primary diagnosis involves inspection of all visible tooth surfaces using a good light source, dental mirror and explorer . Dental radiographs ( X-rays ) may show dental caries before it is otherwise visible, in particular caries between the teeth. Large areas of dental caries are often apparent to the naked eye, but smaller lesions can be difficult to identify. Visual and tactile inspection along with radiographs are employed frequently among dentists, in particular to diagnose pit and fissure caries. Early, uncavitated caries
16764-472: The tertiary structure of the protein, which defines the binding site pocket, and by the chemical properties of the surrounding amino acids' side chains. Protein binding can be extraordinarily tight and specific; for example, the ribonuclease inhibitor protein binds to human angiogenin with a sub-femtomolar dissociation constant (<10 M) but does not bind at all to its amphibian homolog onconase (> 1 M). Extremely minor chemical changes such as
16896-408: The tooth to the surrounding soft tissues . Complications such as cavernous sinus thrombosis and Ludwig angina can be life-threatening. Four things are required for caries to form: a tooth surface (enamel or dentin), caries-causing bacteria, fermentable carbohydrates (such as sucrose ), and time. This involves adherence of food to the teeth and acid creation by the bacteria that makes up
17028-489: The trafficking or secretion of enamel proteins. Therefore, Bcl9, Bcl9l, and Pygo2 have cytoplasmic functions distinct from their roles as transcriptional cofactors downstream of Wnt signaling. This new discovery might improve our understanding for the treatment of human caries . Protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues . Proteins perform
17160-584: The transcription of Wnt target genes. Recent work, using the mouse ( Mus musculus ) and zebrafish ( Danio rerio ) as model organisms, identified an ancient role of BCL9 and BCL9L as key factors required for cardiac development. This work emphasises the tissue-specific nature of the Wnt/β-catenin mechanism of action, and implicates alterations in BCL9 and BCL9L in human congenital heart defects. BCL9 and BCL9L have been shown to take part in other tissue-specific molecular mechanisms, showing that their role in
17292-466: Was insulin , by Frederick Sanger , in 1949. Sanger correctly determined the amino acid sequence of insulin, thus conclusively demonstrating that proteins consisted of linear polymers of amino acids rather than branched chains, colloids , or cyclols . He won the Nobel Prize for this achievement in 1958. Christian Anfinsen 's studies of the oxidative folding process of ribonuclease A, for which he won
17424-581: Was not fully appreciated until 1926, when James B. Sumner showed that the enzyme urease was in fact a protein. Linus Pauling is credited with the successful prediction of regular protein secondary structures based on hydrogen bonding , an idea first put forth by William Astbury in 1933. Later work by Walter Kauzmann on denaturation , based partly on previous studies by Kaj Linderstrøm-Lang , contributed an understanding of protein folding and structure mediated by hydrophobic interactions . The first protein to have its amino acid chain sequenced
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