RopB transcriptional regulator , also known as RopB/Rgg transcriptional regulator is a transcriptional regulator protein that regulates expression of the extracellularly secreted cysteine protease streptococcal pyrogenic exotoxin B (speB or streptopain ), which is an important virulence factor of Streptococcus pyogenes and is responsible for the dissemination of a host of infectious diseases including strep throat , impetigo , streptococcal toxic shock syndrome , necrotizing fasciitis , and scarlet fever . Functional studies suggest that the ropB multigene regulon is responsible for not only global regulation of virulence but also a wide range of functions from stress response, metabolic function, and two-component signaling. Structural studies implicate ropB's regulatory action being reliant on a complex interaction involving quorum sensing with the leaderless peptide signal speB-inducing peptide (SIP) acting in conjunction with a pH sensitive histidine switch.
33-560: Observations of an extracellularly secreted glucosyltransferase (gtfG) sequentially proximal to and activated by an rgg gene with inverted repeats in the intergenic region of Streptococcus gordonii served as a basis for studying its homology between Streptococcus pyogenes . It was discovered that S. pyogenes also shared an rgg/ropB gene located directly next to the subject of its transcriptional regulation, in this case speB protease , with intergenic inverted repeats. Confirmation of linkage between rgg/ropB and speB secretion activation
66-634: A cation (left), whereas addition of an electron gives an anion (right). The hydrogen anion, with its loosely held two-electron cloud, has a larger radius than the neutral atom, which in turn is much larger than the bare proton of the cation. Hydrogen forms the only cation that has no electrons, but even cations that (unlike hydrogen) still retain one or more electrons are still smaller than the neutral atoms or molecules from which they are derived. Hydrogen anions are formed when additional electrons are acquired: Hydrogen ions drive ATP synthase in photosynthesis . This happens when hydrogen ions get pushed across
99-533: A low pH, and subsequently, an acidic product. By definition, an acid is an ion or molecule that can donate a proton, and when introduced to a solution it will react with water molecules (H 2 O) to form a hydronium ion (H 3 O ), a conjugate acid of water. For simplistic reasoning, the hydrogen ion (H ) is often used to abbreviate the hydronium ion. Ocean acidification is the direct consequence of elevated concentrations of hydrogen ions and carbonate saturation from significant absorption of carbon dioxide (CO 2 ) by
132-703: A roughly equivalent secretory control mechanism can be seen in Rgg's regulation of gtfG glucosyltransferase production in S. gordonii , in the manner in which gadR regulates acid resistance in Lactococcus lactis , how lasX regulates expression of lantibiotic lactocin S in Lactobacillus sakei , and mutR's regulation of mutacin in S. mutans . Sequentially, these genes are all localized contiguously to their respective subject of regulation and share promoters localized contiguously to inverted repeat regions. Characterization of
165-432: A slew of other bacteria [See Also: allosteric regulation ]. RopB regulation speB is a key determinant in the expression of the speB proteinase which is a primary virulence factor and the most abundant extracellular protein in streptococcal secretions. SpeB cleaves host serum proteins that make up the human extracellular matrix and bacterial proteins including other secreted streptococcal proteins. As previously mentioned, it
198-441: A type of glycosyltransferase that enable the transfer of glucose . Examples include: They are categorized under EC number 2.4.1. This EC 2.4 enzyme -related article is a stub . You can help Misplaced Pages by expanding it . Hydrogen ion A hydrogen ion is created when a hydrogen atom loses an electron . A positively charged hydrogen ion (or proton ) can readily combine with other particles and therefore
231-583: A union of the α8 - α12 helices of the N-terminal domain and the C-terminal domain. Additionally, there is an Interface I forged from three side chains (C22, Y224, and R226), an Interface II forged from one side chain (I255), and N-terminal domains that are all responsible for dimerizing ropB protein subunits together. The SIP peptide binding pocket is the docking station of the eight amino acid leaderless peptide signal, speB-inducing peptide (SIP). The binding pocket
264-433: A weak diprotic acid. Diprotic acids consist of two ionizable hydrogen atoms in each molecule. In an aqueous solution, partial dissociation of carbonic acid releases a hydrogen proton (H ) and a bicarbonate ion (HCO 3 ), and subsequently, the bicarbonate ion dissociates into an additional hydrogen proton and a carbonate ion (CO 3 ). The dissolving and dissociating of these inorganic carbon species generate an increase in
297-419: Is 59 times higher than in the atmosphere; the ocean acts as the largest carbon sink on the planet, playing a significant role in climate regulation. In addition to carbon fluxes, the natural process of carbon sequestration from the atmosphere into the deep ocean is facilitated by two systems, the biological pump and the solubility pump. The solubility pump is a physico-chemical process that transfers CO 2 at
330-476: Is a tripartite construction of the C-terminal's α12 helix which is a capping helix, TPR3's α6 helix that has a hydrophobic interplay with SIP sidechains, and TPR 4's α8 helix which electrostatically stabilizes SIP. Variations in pH level altered strength of adherence between SIP and the SIP binding pocket with acidic pH levels between 5.5 and 6.5 enhancing adherence and pH levels between 7 and 9 reducing adherence. Though
363-405: Is only seen isolated when it is in a gaseous state or a nearly particle-free space. Due to its extremely high charge density of approximately 2×10 times that of a sodium ion, the bare hydrogen ion cannot exist freely in solution as it readily hydrates, i.e., bonds quickly. The hydrogen ion is recommended by IUPAC as a general term for all ions of hydrogen and its isotopes . Depending on
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#1732931813818396-426: Is responsible for the dissemination of a host of infectious diseases including but not limited to pharyngitis , impetigo , streptococcal toxic shock syndrome , necrotizing fasciitis , and scarlet fever . Therefore, study of the inactivation of speB's many functional pathways and regulators are of critical importance in developing potential novel therapeutics. Glucosyltransferase Glucosyltransferases are
429-404: The charge of the ion, two different classes can be distinguished: positively charged ions and negatively charged ions. A hydrogen atom is made up of a nucleus with charge +1, and a single electron. Therefore, the only positively charged ion possible has charge +1. It is noted H . Depending on the isotope in question, the hydrogen cation has different names: In addition, the ions produced by
462-450: The N-domain while the rest lie in the C-terminal domain. Streptococcus pyogenes has evolved an interwoven complex of gene regulatory mechanisms in the SIP signaling pathway by implanting a pH sensitive histidine switch onto the quorum-sensing ropB protein. During the neutral to basic pH conditions whether synthetically induced or naturally caused by low population density of S. pyogenes ,
495-522: The N-terminal. The C-terminal domain, also known as ropB-CTD, is a carboxy terminal ligand-binding domain made of amino acids 56–280. RopB-CTD houses 5 TPR motifs and attaches to the SIP peptide in the innermost part of the SIP binding pocket in a sequence-specific manner without induction of polymerization . The tetratricopeptide repeat domain provides the concave surface necessitated for SIP recognition. RopB-CTD houses 5 stacked TPR motifs, each having sets of paired antiparallel helices that aid in
528-804: The RRNPP family of quorum-sensing regulators (which stands for proteins Rap, NprR, PrgX, PlcRd) were used in comparisons with ropB to postulate its structural functions. The Rap protein derived from Bacilli regulates sporulation , the NprR protein in Bacillus thuringiensis regulates necrotrophism, the PrgX protein regulates conjugation in Enterococcus faecalis , and PlcR protein regulates transcription of virulence factors in both Bacillis thuringiensis and Bacillus cereus . Similarities were observed in conserved asparagine residues on
561-496: The SIP pathway to allow for the SIP-ropB protein complex to form and increasing SIP production. Furthermore, increased cytosolic acidity enhances the maturation of speB zymogen (speBz) into mature speB protease (speBm) to dramatically increase its proteolytic activity and virulence. Rgg-like transcriptional regulators can be found in a variety of gram-positive bacteria . Where ropB regulates speB protease production in S. pyogenes ,
594-575: The TPR motifs of each of these proteins and in ropB. Quorum sensing regulates a menagerie of aspects in Bacillota including the production of ropB-like proteins in Streptococcus pneumoniae and S. pyogenes . Similarities in the pH sensitivity of the cell signaling mechanisms were found in pneumococci , S. mutans , and Staphylococcus aureus as well. Amongst Rgg-like proteins, it has been observed that
627-480: The air-sea interface. Based on Henry's Law, the amount of dissolved CO 2 in an aqueous solution is directly proportional to the partial pressure of CO 2 in the atmosphere. To maintain equilibrium, a state of high atmospheric partial pressure of CO 2 leads to an increased oceanic exchange of this gas by molecular diffusion. In the surface waters, dissolved atmospheric carbon dioxide (CO 2(aq) ) reacts with water molecules to form carbonic acid (H 2 CO 3 ),
660-493: The buffering capacity threshold, consequently resulting in higher rates of ocean acidification. Shifts in the ocean's carbonate chemistry has the potential to manipulate ocean biogeochemical cycles for many elements and compounds causing profound impacts on marine ecosystems. Furthermore, the solubility of CO 2 is temperature dependent; elevated surface water temperatures reduce CO 2 solubility. A continual rise in atmospheric partial pressure of CO 2 could potentially convert
693-411: The concentration of hydrogen ions and inversely lowers ambient surface ocean pH. The carbonate buffering system governs the acidity of seawater by maintaining dissolved inorganic carbon species in chemical equilibrium. The chemical equation consists of reactants and products that may react in either direction. More reactants added to a system yield more product production (the chemical reaction shifts to
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#1732931813818726-415: The formation of a concave inner pathway and a convex exterior. The base of the recognition site is constructed by alpha helices α6 and α8, while the supporting walls are constructed from helices α2, and α12. The exterior portion of the recognition site is flanked by asparagines N152 and N192, thus providing a ridge of support for the peptide-protein complex. The dimer interfaces of ropB are constructed by
759-470: The gene itself inside the highly repetitive intergenic region. The ropB protein binding location lies adjacent to speB promoter 1 that is also located within the highly repetitive intergenic region, although the ropB gene and the speB gene are transcribed in opposite directions. The -10 and -35 regions of speB promoter 1 have poor consensus ; in order to ameliorate this, the ropB aids the RNA polymerase bondage with
792-482: The help of a polyU polypyrimidine tract inside the palindromic inverted repeat region in a fashion uncannily similar to intrinsic termination in E. coli . The N-terminal domain consists of amino acids 1-56 and is an amino terminal responsible for DNA-binding and is a key mediator in the linkage between the C-terminal domain of the opposite dimer . The dimer interface II has its I255 side chain located in
825-423: The inner membrane of the mitochondria . Hydrogen ions concentration, measured as pH, is also responsible for the acidic or basic nature of a compound. Water molecules split to form H and hydroxide anions. This process is referred to as the self-ionization of water . The concentration of hydrogen ions and pH are inversely proportional; in an aqueous solution, an increased concentration of hydrogen ions yields
858-537: The interaction between the unprotonated functionally involved histidine (H144) with relevant sidechains (Y176, Y182, E185) in the SIP binding pocket domain is impaired and speB protease expression is inhibited. On the other hand, as extracellular pH decreases to be more acidic in cases of high population density, S. pyogenes has no elaborate pH homeostatic capabilities relative to non-lactic bacteria, therefore intracellular cytosolic pH levels will more easily resemble extracellular levels. Cytosolic acidification mobilizes
891-466: The membrane creating a high concentration inside the thylakoid membrane and a low concentration in the cytoplasm. However, because of osmosis, the H will force itself out of the membrane through ATP synthase. Using their kinetic energy to escape, the protons will spin the ATP synthase which in turn will create ATP . This happens in cellular respiration as well though the concentrated membrane will instead be
924-416: The pH sensitive histidine (particularly H144) and interacting amino acids (Y176, Y182, and E185) of ropB of Streptococcus pyogenes are conserved in S. porcinus , S. pseudoporcinus , S. salivarius , L. pentosus , L. aviaries , L. reuteri , and Enterococcus sp. including E. faecalis . Thus, suggesting the usage of a pH sensitive histidine switch complex with gene-regulating effector molecules in
957-465: The reaction of these cations with water as well as their hydrates are called hydrogen ions: Zundel cations and Eigen cations play an important role in proton diffusion according to the Grotthuss mechanism . In connection with acids, "hydrogen ions" typically refers to hydrons. In the image at left the hydrogen atom (center) contains a single proton and a single electron. Removal of the electron gives
990-583: The right) and if more product is added, additional reactants will form, shifting the chemical reaction to the left. Therefore, in this model, a high concentration of the beginning reactant, carbon dioxide, produces an increased amount of end-product (H and CO 3 ), thus lowering pH and creating a more acidic solution. The natural buffering system of the ocean resist the change in pH by producing more bicarbonate ions generated by free acid protons reacting with carbonate ions to form an alkaline character. However, increasing atmospheric CO 2 concentrations may exceed
1023-401: The ropB protein has seven histidines (H12, H81, H93, H144, H265, H266, and H277) structurally present, the ropB histidine switch primarily operates with a single functionally involved histidine (H144) conveniently placed to associate with ropB sidechains (Y176 and E185) that near each other upon the addition of a hydrogen ion to H144 in acidic conditions. Only one histidine (H12) is located on
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1056-413: The world's oceans. The pre-industrial state of the ocean's carbonate chemistry has been notably stable, including the balance of its pH. Following the industrial revolution, anthropogenic emissions of burning fossil fuels , cement production, and changes in land use, have increased the oceans uptake of carbon dioxide from the atmosphere by 30%. In the ocean, the absorption capacity of this greenhouse gas
1089-440: Was achieved by means of ropB insertional disruption which resulted in decreased speB production. The location of the ropB gene is directly and sequentially proximal to the subject of its transcriptional regulation, speB, which lies downstream of a 941 bp intergenic region between the two. Transcription of the ropB gene seems to necessitate a promoter within a series sequences between 238 and 480 bp and up to 800 bp upstream of
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