Sandbox WWC6: Difference between revisions
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[[Hemolysins]] [https://en.wikipedia.org/wiki/Hemolysin#.CE.B1-hemolysin] are a lipid or protein toxins secreted by pathogens that lyse erythrocyte and some bacterial cell membranes. These toxins belong to a family of microbial exotoxins called cytolysins, which act on a broad number of cells[http://www.uniprot.org/uniprot/P09616]. The primary function of peptide hemolysins is pore formation at the cell membranes creating acytolytic effect, and is achieved by the release of cytosolic | [[Hemolysins]] [https://en.wikipedia.org/wiki/Hemolysin#.CE.B1-hemolysin] are a lipid or protein toxins secreted by pathogens that lyse erythrocyte and some bacterial cell membranes. These toxins belong to a family of microbial exotoxins called cytolysins, which act on a broad number of cells[http://www.uniprot.org/uniprot/P09616]. The primary function of peptide hemolysins is pore formation at the cell membranes creating acytolytic effect, and is achieved by the release of cytosolic ions and small molecules through the hydrophilic, transmembrane portion of the beta-barrel pore[http://www.sciencedirect.com/science/article/pii/S0041010101001532]. | ||
<Structure load='7AHL' size='350' frame='true' align='right' caption='Stapholococcal alpha-hemolysin' scene='Insert optional scene name here' /> | <Structure load='7AHL' size='350' frame='true' align='right' caption='Stapholococcal alpha-hemolysin' scene='Insert optional scene name here' /> | ||
== Function == | == Function == | ||
Hemolysins are most commonly proteins found in red blood cells that selectively allow for the diffusion of potassium ions across the membrane. <ref >https://en.wikipedia.org/wiki/Hemolysin#cite_note-pmid20692229-3</ref> or lipid biosurfactants that disrupt membrane composition resulting in cell lysis. These proteins are important for some erythrocyte nutrient accession, but cause massive erythrocyte destruction in bacterial infection, specifically responsible forhemolytic anemia, which causes fatigue, pain, arrythmias, and even heart failure in affected individuals.<ref>http://www.nhlbi.nih.gov/health/health-topics/topics/ha/</ref | Hemolysins are most commonly proteins found in red blood cells that selectively allow for the diffusion of potassium ions across the membrane. <ref >https://en.wikipedia.org/wiki/Hemolysin#cite_note-pmid20692229-3</ref> or lipid biosurfactants that disrupt membrane composition resulting in cell lysis. These proteins are important for some erythrocyte nutrient accession, but cause massive erythrocyte destruction in bacterial infection, specifically responsible forhemolytic anemia, which causes fatigue, pain, arrythmias, and even heart failure in affected individuals.<ref>http://www.nhlbi.nih.gov/health/health-topics/topics/ha/</ref> | ||
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Pore-forming toxins have been shown to closely relate to the pathogenicity of the toxin-producing organism <ref>http://www.ncbi.nlm.nih.gov/pubmed/1930675<ref> Both gram positive and gram negative bacteria are producers of hemolysins, as well as some clinically relevant fungi. Toxin secretion facillitates the availability of water, ions, and small molecules like sugar for the secreting pathogen. | Pore-forming toxins have been shown to closely relate to the pathogenicity of the toxin-producing organism <ref>http://www.ncbi.nlm.nih.gov/pubmed/1930675<ref> Both gram positive and gram negative bacteria are producers of hemolysins, as well as some clinically relevant fungi. Toxin secretion facillitates the availability of water, ions, and small molecules like sugar for the secreting pathogen. | ||
== Mechanism of action == | == Mechanism of action == | ||
Four of each of the two subunits assemble in an alternating, circular pattern in the γ-HL pore, whereas seven distinct α-HL protomers assemble in a circular arrangement in the α-HL pore. These typically are comprised of three domains: the cap, rim and stem domains, named for the structural resemblance to a mushroom. The cap domain contains β-sandwiches from each protomer, while just below, the rim domain contains four looping β-strands. The stem domain takes on the antiparallel β-barrel, a portion of which becomes the transmembrane structure. | Four of each of the two subunits assemble in an alternating, circular pattern in the γ-HL pore, whereas seven distinct α-HL protomers assemble in a circular arrangement in the α-HL pore. These typically are comprised of three domains: the cap, rim and stem domains, named for the structural resemblance to a mushroom. The cap domain contains β-sandwiches from each protomer, while just below, the rim domain contains four looping β-strands. The stem domain takes on the antiparallel β-barrel, a portion of which becomes the transmembrane structure. | ||
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===Pore formation=== | ===Pore formation=== | ||
Studies suggest that pore formation is achieved through a nonlytic intermediate oligomer, known as a prepore. The prepore model proposal suggests that the monomeric components assemble on the cell membrane surfacte into a prepore with prestem subunits packed inside. The formed prepore then goes through a conformational change prestem, forming the β-barrel pore. Several issues with the proposed pore formation mechanism have been identified including steric hindrance of the packed prestem structure. | Studies suggest that pore formation is achieved through a nonlytic intermediate oligomer, known as a prepore. The prepore model proposal suggests that the monomeric components assemble on the cell membrane surfacte into a prepore with prestem subunits packed inside. The formed prepore then goes through a conformational change prestem, forming the β-barrel pore. Several issues with the proposed pore formation mechanism have been identified including steric hindrance of the packed prestem structure. | ||
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===Role in infection=== | ===Role in infection=== | ||
There are nine different α subunits named NaV1.1 through NAV1.9. <ref name = "sod"/> Genes are SCN1 through SCN11. <ref name = "sod"/> These structures differ in their sequence and kinetics. <ref name = "sod"/> As stated above, the α subunit is necessary to the function of the channel and can function independently of the β subunit. You can find the structures and more information below. | There are nine different α subunits named NaV1.1 through NAV1.9. <ref name = "sod"/> Genes are SCN1 through SCN11. <ref name = "sod"/> These structures differ in their sequence and kinetics. <ref name = "sod"/> As stated above, the α subunit is necessary to the function of the channel and can function independently of the β subunit. You can find the structures and more information below. | ||
