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109-451: 3TT9 ,%%s 3TT9 5318 67451 ENSG00000057294 ENSMUSG00000041957 Q99959 Q9CQ73 NM_004572 NM_001005242 NM_026163 NP_001005242 NP_004563 NP_080439 Plakophilin-2 is a protein that in humans is encoded by the PKP2 gene . Plakophilin 2 is expressed in skin and cardiac muscle , where it functions to link cadherins to intermediate filaments in

218-438: A , {\displaystyle a,} b , {\displaystyle b,} and c {\displaystyle c} are constants depending on the architecture of tissue. Using scanning electron microscopy, it was found that the variation in trabecular architecture with different anatomic sites lead to different modulus. To understand structure-anisotropy and material property relations, one must correlate

327-516: 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

436-470: 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.

545-408: A stimulus to the trabecular, changing its geometry so as to sustain or mitigate strain loads. By using finite element modelling, a study tested four different species under an equal apparent stress (σapp) to show that trabecular scaling in animals alters the strain within the trabecular. It was observed that the strain within trabeculae from each species varied with the geometry of the trabeculae. From

654-428: A cell filter (as in the trabecular meshwork of the eye ). Trabecular bone, also called cancellous bone , is porous bone composed of trabeculated bone tissue. It can be found at the ends of long bones like the femur, where the bone is actually not solid but is full of holes connected by thin rods and plates of bone tissue. The holes (the volume not directly occupied by bone trabecula) is the intertrabecular space , and

763-552: 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,

872-403: 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

981-834: 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

1090-485: A direction at which mechanical stiffness and strength are greatest. Because of the microstructural directionality, the mechanical properties of trabecular bone are highly anisotropic. The range of Young's modulus for trabecular bone is 800 to 14,000 MPa and the strength of failure is 1 to 100 MPa. As mentioned above, the mechanical properties of trabecular bone are very sensitive to apparent density. The relationship between modulus of trabecular bone and its apparent density

1199-486: A highly sensitive and specific diagnostic indicator. Clinical and genetic characterization of arrhythmogenic right ventricular cardiomyopathy is currently under intense investigation to understand the penetrance associated with PKP2 mutations, as well as other genes encoding desmosomal proteins, in disease progression and outcome. PKP2 mutations were also found to coexist with sodium channelopathies in patients with Brugada syndrome . Additionally, plakophilin-2

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1308-637: A human reaches adulthood, bone density steadily decreases with age, to which loss of trabecular bone mass is a partial contributor. Loss of bone mass is defined by the World Health Organization as osteopenia if bone mineral density (BMD) is one standard deviation below mean BMD in young adults, and is defined as osteoporosis if it is more than 2.5 standard deviations below the mean. A low bone density greatly increases risk for stress fracture , which can occur without warning. The resulting low-impact fractures from osteoporosis most commonly occur in

1417-478: 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

1526-410: 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

1635-500: 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

1744-411: 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

1853-539: 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

1962-486: 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

2071-421: A role in the diffusion of nutrients and waste products of osteocytes by regulating the distance between osteocytes and bone surface to approximately 230 μm. Due to an increased reduction of blood oxygen saturation, animals with high metabolic demands tend to have a lower trabecular thickness (Tb.Th) because they require increased vascular perfusion of trabeculae. The vascularization by tunneling osteons changes

2180-630: A scale of tens of micrometers, which is approximately the size of osteocytes , the figure below shows that thicker trabeculae exhibited less strain. The relative frequency distributions of element strain experienced by each species shows a higher elastic moduli of the trabeculae as the species size increases. Additionally, trabeculae in larger animals are thicker, further apart, and less densely connected than those in smaller animals. Intra-trabecular osteon can commonly be found in thick trabeculae of larger animals, as well as thinner trabeculae of smaller animals such as cheetah and lemurs . The osteons play

2289-406: 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 "),

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2398-566: A shift in gating and kinetics; pharmacological challenge also induced ventricular arrhythmias . These findings further support the notion that desmosomes crosstalk with sodium channels in the heart, and suggest that the risk of arrhythmias in patients with PKP2 mutations may be unveiled with pharmacological challenge. Evidence has also shown that plakophilin-2 binds to the K(ATP) channel subunit, Kir6.2 , and that in cardiomyocytes from haploinsufficient PKP2 mice, K(ATP) channel current density

2507-432: 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

2616-451: 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

2725-441: 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

2834-432: 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

2943-511: Is a member of the armadillo repeat and plakophilin protein family. Plakophilin proteins contain nine central, conserved armadillo repeat domains flanked by N-terminal and C-terminal domains. Alternately spliced transcripts encoding protein isoforms have been identified. Plakophilin 2 localizes to cell desmosomes and nuclei and binds plakoglobin , desmoplakin , and the desmosomal cadherins via N-terminal head domain. Plakophilin 2 functions to link cadherins to intermediate filaments in

3052-413: 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. Trabeculae Cancellous bone

3161-761: Is estimated that 70% of all mutations associated with arrhythmogenic right ventricular cardiomyopathy are within the PKP2 gene . These mutations in general appear to disrupt the assembly and stability of desmosomes . Mechanistic studies have shown that certain PKP2 mutations result in instability of the plakophilin-2 protein due to enhanced calpain -mediated degradation. Specific and sensitive markers of PKP2 and plakoglobin mutation carriers in arrhythmogenic right ventricular cardiomyopathy have been identified to include T-wave inversions, right ventricular wall motion abnormalities, and ventricular extrasystoles . Additionally, immunohistochemical analysis of proteins comprising cardiomyocyte desmosomes has shown to be

3270-478: Is formed from groupings of trabeculated bone tissue. In cross section, trabeculae of a cancellous bone can look like septa , but in three dimensions they are topologically distinct, with trabeculae being roughly rod or pillar-shaped and septa being sheet-like. When crossing fluid-filled spaces, trabeculae may offer the function of resisting tension (as in the penis , see for example trabeculae of corpora cavernosa and trabeculae of corpus spongiosum ) or providing

3379-628: 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

Plakophilin-2 - Misplaced Pages Continue

3488-469: 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"

3597-461: 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

3706-670: Is necessary for normal localization and content of desmoplakin to desmosomes , which may in part be due to the recruitment of protein kinase C alpha to desmoplakin . Ablation of PKP2 in mice severely disrupts normal heart morphogenesis. Mutant mice are embryonic lethal and exhibit deficits in the formation of adhering junctions in cardiomyocytes , including the dissociation of desmoplakin and formation of cytoplasmic granular aggregates around embryonic day 10.5-11. Additional malformation included reduced trabeculation , cytoskeletal disarray and cardiac wall rupture. Further studies demonstrated that plakophilin-2 coordinate with E-cadherin

3815-460: Is occupied by red bone marrow , where all the blood cells are made, as well as fibrous tissue. Even though trabecular bone contains a lot of intertrabecular space, its spatial complexity contributes the maximal strength with minimum mass. It is noted that the form and structure of trabecular bone are organized to optimally resist loads imposed by functional activities, like jumping, running and squatting. And according to Wolff's law , proposed in 1892,

3924-404: 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

4033-555: Is required to properly localize RhoA early in actin cytoskeletal rearrangement in order to properly couple the assembly of adherens junctions to the translocation of desmosome precursors in newly formed cell-cell junctions. Plakophilin-2 over time has shown to be more than components of cell-cell junctions; rather the plakophilins are emerging as versatile scaffolds for various signaling pathways that more globally modulate diverse cellular activities. Plakophilin-2 has shown to localize to nuclei, in addition to desmosomal plaques in

4142-532: 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

4251-474: Is the linear region where individual trabecula bend and compress as the bulk tissue is compressed. The second stage occurs after yielding, where trabecular bonds start to fracture, and the final stage is the stiffening stage. Typically, lower density trabecular areas offer more deformed staging before stiffening than higher density specimens. In summary, trabecular bone is very compliant and heterogeneous. The heterogeneous character makes it difficult to summarize

4360-415: Is thicker and more individual trabeculae. Relative to the trabeculae in lark, the woodpecker's trabecular is more closely spaced and more plate-like. [19] These properties result in higher ultimate strength in the cranial bone of the woodpecker. The diminutive form of Latin trabs , means a beam or bar. In the 19th century, the neologism trabeculum (with an assumed plural of trabecula ) became popular, but

4469-476: Is under excessive stress and degrades over time, causing stiffness, pain, and loss of movement. With osteoarthritis, the underlying bone plays a significant role in cartilage degradation. Thus any trabecular degradation can significantly affect stress distribution and adversely affect the cartilage in question. Due to its strong effect on overall bone strength, there is currently strong speculation that analysis in patterns of trabeculae degradation may be useful in

Plakophilin-2 - Misplaced Pages Continue

4578-475: The Na(V)1.5 complex, ankyrin G , and loss of ankyrin G via siRNA downregulation mislocalized plakophilin-2 and connexin 43 in cardiac cells, which was coordinate with decreased electrical coupling of cells and decreased adhesion strength. These studies were further supported by an investigation in a mouse model harboring a PKP2 - heterozygous null mutation, which showed decreased Na(V)1.5 amplitude, as well as

4687-486: 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

4796-453: The cytoplasm . Studies have shown that plakkophillin-2 is found in the nucleoplasm, complexed in the RNA polymerase III holoenzyme with the largest subunit of RNA polymerase III, termed RPC155 . There are data to support molecular crosstalk between plakophilin-2 and proteins involved in mechanical junctions in cardiomyocytes , including connexin 43 , the major component of cardiac gap junctions ;

4905-540: The cytoskeleton . In cardiac muscle , plakophilin-2 is found in desmosome structures located within intercalated discs . Mutations in PKP2 have been shown to be causal in arrhythmogenic right ventricular cardiomyopathy . Two splice variants of the PKP2 gene have been identified. The first has a molecular weight of 97.4 kDa (881 amino acids ) and the second of molecular weight of 92.7 kDa (837 amino acids ). A processed pseudogene with high similarity to this locus has been mapped to chromosome 12p13. Plakophilin-2

5014-644: 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

5123-645: 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,

5232-461: The upper femur , which consists of 25-50% trabecular bone depending on the region, in the vertebrae , which are about 90% trabecular, or in the wrist . When trabecular bone volume decreases, its original plate-and-rod structure is disturbed; plate-like structures are converted to rod-like structures and pre-existing rod-like structures thin until they disconnect and resorb into the body. Changes in trabecular bone are typically gender-specific, with

5341-493: 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

5450-562: 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

5559-498: 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 )

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5668-516: 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

5777-709: 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

5886-405: 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

5995-595: 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

6104-531: 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

6213-408: The amount of bone per unit volume or by altering the geometry and arrangement of individual trabeculae as body size and bone loading increases. Trabecular bone scales allometrically , reorganizing the bones' internal structure to increase the ability of the skeleton to sustain loads experienced by the trabeculae. Furthermore, scaling of trabecular geometry can moderate trabecular strain. Load acts as

6322-476: The beak has a lesser role in impact absorption. One measured advantage of the woodpecker's beak is the slight overbite (upper beak is 1.6mm longer than lower beak) which offers a bimodal distribution of force due to the asymmetric surface contact. The staggered timing of impact induces a lower strain on the trabeculae in the forehead, occiput, and beak. The larger the animal, the higher the load forces on its bones. Trabecular bone increases stiffness by increasing

6431-574: 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 ,

6540-570: 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

6649-558: 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

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6758-436: 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

6867-752: 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

6976-450: 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

7085-621: 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

7194-441: 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

7303-490: 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

7412-455: The cytoskeleton. In cardiomyocytes , plakophilin-2 is found at desmosome structures within intercalated discs , which link adjacent sarcolemmal membranes together. The desmosomal protein , desmoplakin , is the core constituent of the plaque which anchors intermediate filaments to the sarcolemma by its C-terminus and indirectly to sarcolemmal cadherins by its N-terminus , facilitated by plakoglobin and plakophilin-2. Plakophilin

7521-408: 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

7630-427: The differences in trabecular geometry in the femoral head and condyle could be attributed to different loading environments of coxofemoral and femorotibial joints . The woodpecker 's ability to resist repetitive head impact is correlated with its unique micro/nano-hierarchical composite structures. Microstructure and nanostructure of the woodpecker's skull consists of an uneven distribution of spongy bone ,

7739-414: The distribution of trabeculae in bird species is uneven and is dependent on load conditions. The bird with the highest density of trabeculae is the kiwi , a flightless bird. There is also uneven distribution of trabeculae within similar species such as the great spotted woodpecker or grey-headed woodpecker . After examining a micro CT scan of the woodpecker's forehead, temporomandibulum, and occiput it

7848-447: 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

7957-475: The external shape and internal architecture of bone are determined by external stresses acting on it. The internal structure of the trabecular bone firstly undergoes adaptive changes along stress direction and then the external shape of cortical bone undergoes secondary changes. Finally bone structure becomes thicker and denser to resist external loading. Because of the increased occurrence of total joint replacement and its impact on bone remodeling, understanding

8066-422: The general mechanical properties for trabecular bone. High porosity makes trabecular bone compliant and large variations in architecture leads to high heterogeneity. The modulus and strength vary inversely with porosity and are highly dependent on the porosity structure. The effects of aging and small cracking of trabecular bone on its mechanical properties are a source of further study. Studies have shown that once

8175-525: 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

8284-478: 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

8393-443: 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

8502-457: The measured mechanical properties of anisotropic trabecular specimens with the stereological descriptions of their architecture. The compressive strength of trabecular bone is also very important because it is believed that the inside failure of trabecular bone arise from compressive stress. On the stress-strain curves for both trabecular bone and cortical bone with different apparent density, there are three stages in stress-strain curve. The first

8611-405: 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

8720-431: The most notable differences in bone mass and trabecular microstructure occurring within the age range for menopause. Trabeculae degradation over time causes a decrease in bone strength that is disproportionately large in comparison to volume of trabecular bone loss, leaving the remaining bone vulnerable to fracture. With osteoporosis there are often also symptoms of osteoarthritis , which occurs when cartilage in joints

8829-432: The near future in tracking the progression of osteoporosis. The hollow design of bird bones is multifunctional. It establishes high specific strength and supplements open airways to accommodate the skeletal pneumaticity common to many birds. The specific strength and resistance to buckling is optimized through a bone design that combines a thin, hard shell that encases a spongy core of trabeculae. The allometry of

8938-496: 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

9047-500: 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

9156-415: The organizational shape of individual trabeculae. This affects the woodpecker's mechanical properties, allowing the cranial bone to withstand a high ultimate strength (σu). Compared to the cranial bone of the lark , the woodpecker's cranial bone is denser and less spongy, having a more plate-like structure rather than the more rod-like structure observed in larks. Furthermore, the woodpecker's cranial bone

9265-440: 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

9374-422: The physiological cost of producing, maintaining, and moving tissue. However, BV/TV showed significant positive scaling in avian femoral condyles . Larger birds present decreased flight habits due to avian BV/TV allometry. The flightless kiwi, weighing only 1–2 kg, had the greatest BV/TV of the birds tested in the study. This shows that trabecular bone geometry is related to ‘prevailing mechanical conditions’, so

9483-400: The porosity percent of trabecular bone is in the range 75–95% and the density ranges from 0.2 to 0.8 g/cm . It is noted that the porosity can reduce the strength of the bone, but also reduce its weight. The porosity and the manner that porosity is structured affect the strength of material. Thus, the micro structure of trabecular bone is typically oriented and ''grain'' of porosity is aligned in

9592-424: 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

9701-534: 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,

9810-427: 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

9919-582: 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

10028-573: 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

10137-430: 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

10246-436: The shell of the beak, but to a lesser extent compared to the skull. As a result of fewer trabeculae in the beak, the beak has a higher stiffness (1.0 GPa) compared to the skull (0.31 GPa). While the beak absorbs some of the impact from pecking, most of the impact is transferred to the skull where more trabeculae are actively available to absorb the shock. The ultimate strength of woodpeckers' and larks' beaks are similar, inferring

10355-506: The stress-related and adaptive process of trabecular bone has become a central concern for bone physiologists. To understand the role of trabecular bone in age-related bone structure and in the design for bone-implant systems, it is important to study the mechanical properties of trabecular bone as a function of variables such as anatomic site, bone density, and age related issues. Mechanical factors including modulus, uniaxial strength, and fatigue properties must be taken into account. Typically,

10464-405: 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

10573-706: 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

10682-400: 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

10791-472: 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

10900-409: The trabeculae allows the skeleton to tolerate loads without significantly increasing the bone mass. The red-tailed hawk optimizes its weight with a repeating pattern of V-shaped struts that give the bones the necessary lightweight and stiff characteristics. The inner network of trabeculae shifts mass away from the neutral axis , which ultimately increases the resistance to buckling . As in humans,

11009-406: The trabecular geometry from solid to tube-like, increasing bending stiffness for individual trabeculae and sustaining blood supply to deep tissue osteocytes. Bone volume fraction (BV/TV) was found to be relatively constant for the variety of animal sizes tested. Larger animals did not show a significantly larger mass per unit volume of trabecular bone. This may be due to an adaptation which reduces

11118-665: The voltage-gated sodium channel Na(V)1.5 and its interacting subunit, ankyrin G ; and the K(ATP) . Decreased expression of plakophilin-2 via siRNA leads to a decrease in and redistribution of connexin 43 protein , as well as a decrease in coupling of adjacent cardiomyocytes . Studies also showed that GJA1 and plakophilin-2 are components in the same biomolecular complex . Plakophilin-2 also associates with Na(V)1.5 , and knockdown of plakophilin-2 in cardiomyocytes alters sodium current properties as well as velocity of action potential propagation. It has also been demonstrated that plakophilin-2 associates with an important component of

11227-453: The woodpecker's brain has been attributed to the higher quantity of thicker plate-like struts packed more closely together than the hawk or hoopoe or the lark. Conversely, the thinner rod-like structures would lead to greater deformation. A destructive mechanical test with 12 samples show the woodpecker's trabeculae design has an average ultimate strength of 6.38MPa, compared to the lark's 0.55MPa. Woodpeckers' beaks have tiny struts supporting

11336-466: 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

11445-423: Was demonstrated by Carter and Hayes in 1976. The resulting equation states: E = a + b ⋅ ρ c {\displaystyle E=a+b\cdot \rho ^{c}} where E {\displaystyle E} represents the modulus of trabecular bone in any loading direction, ρ {\displaystyle \rho } represents the apparent density, and

11554-485: Was determined that there is significantly more trabeculae in the forehead and occiput. Besides the difference in distribution, the aspect ratio of the individual struts was higher in woodpeckers than in other birds of similar size such as the Eurasian hoopoe or the lark . The woodpeckers' trabeculae are more plate-like while the hawk and lark have rod-like structures networked through their bones. The decrease in strain on

11663-487: Was found in adherens junctions of cardiac myxomata tumors analyzed, and absent in patients with noncardiac myxomata , suggesting that plakophilin-2 may serve as a valuable marker in the clinical diagnosis of cardiac myxomata . PKP2 has been shown to interact with: Protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues . Proteins perform

11772-581: 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

11881-495: Was ~40% smaller and regional heterogeneity of K(ATP) channels was altered, suggesting that plakophilin-2 interacts with K(ATP) and mediates crosstalk between intercellular junctions and membrane excitability. Mutations in PKP2 have been associated with, have been shown to cause, and are considered common in arrhythmogenic right ventricular cardiomyopathy , which is characterized by fibrofatty replacement of cardiomyocytes , ventricular tachycardia and sudden cardiac death . It

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