Sandbox WWC6: Difference between revisions
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==Structure== | ==Structure== | ||
Hemolysins have three structural variations: alpha, beta, and gamma. These hemolysin types are comprised of di-, hepta- or octomeric subunits. | Hemolysins have three structural variations: alpha, beta, and gamma. These hemolysin types are comprised of di-, hepta- or octomeric subunits. | ||
===Alpha-hemolysin=== | ===Alpha-hemolysin=== | ||
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<scene name='69/696302/Alpha-hemolysin/1'>Alpha-hemolysin</scene> | <scene name='69/696302/Alpha-hemolysin/1'>Alpha-hemolysin</scene> | ||
Alpha hemolysins cause a partial lysis of red blood cells. | Alpha hemolysins cause a partial lysis of red blood cells. The heptameric pore assembles from water-soluble subunits. The alpha subunit, depicted right, consists seven identical monomeric units that exhibit rotational symmetry in oligomerized form. Each distinct subunit is differently colored for easy identification. The beta-barrel transmembrane domain is 50 Å in length <ref>http://www.ks.uiuc.edu/Research/hemolysin/<ref>. | ||
The heptameric pore assembles from water-soluble subunits The | |||
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==Mechanism | ==Mechanism== | ||
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. | ||
===Pore formation=== | ===Pore formation=== | ||
Pore formation of hemolysins is believed to be a conserved process accross subtypes <ref>http://www.nature.com/ncomms/2014/140929/ncomms5897/full/ncomms5897.html<ref> | |||
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. | ||
Revision as of 14:29, 13 May 2016
HemolysinHemolysin
Hemolysins [1] 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[2]. 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[3].
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FunctionFunction
Hemolysins are most commonly proteins found in red blood cells that selectively allow for the diffusion of potassium ions across the membrane. [1] or lipid biosurfactants that disrupt membrane composition resulting in cell lysis. Hemolysins act through disruption of the cell membrane. [2] Pore formation[3] is the olgomerization of the pore sunbunits within the membrane. The pore is quickly filled with water, ions, and small molecules that rapidly exit the cell, dissipating ionic gradients and membrane potential. Osmotic pressure causes a rapid swelling of the cell, leading to total rupture of the membrane Cite error: Closing </ref> missing for <ref> tag
StructureStructure
Hemolysins have three structural variations: alpha, beta, and gamma. These hemolysin types are comprised of di-, hepta- or octomeric subunits.
Alpha-hemolysinAlpha-hemolysin
Alpha hemolysins cause a partial lysis of red blood cells. The heptameric pore assembles from water-soluble subunits. The alpha subunit, depicted right, consists seven identical monomeric units that exhibit rotational symmetry in oligomerized form. Each distinct subunit is differently colored for easy identification. The beta-barrel transmembrane domain is 50 Å in length Cite error: Closing </ref> missing for <ref> tag
Role in infectionRole in infection
Hemolysin lysis of red blood cells is a marker for many kinds of pathogenic infection characterized by...
OncologyOncology
This disease causes seizures, fainting or sudden death from cardiac arrhythmias and is caused my a mutation in the SCN5A gene, or the gene that encodes the NaV1.5 alpha subunit. [4][5] It was found that this deletion includes residues 1505-1507 (KPQ).[4] These residues occur in the cytoplasmic linker between domain III and domain IV. [4]
Hemolytic anemiaHemolytic anemia
Hemolytic anemia occurs when lysis of red blood cells occurs are rates faster than they can be replaced by bone marrow. <ref>https://www.nhlbi.nih.gov/health/health-topics/topics/ha<ref>
Marker for fungi exposureMarker for fungi exposure
Many indoor fungi have been shown to produse both alpha and beta-hemolysins. The treatment of blood samples with
TreatmentTreatment
ReferencesReferences
- ↑ https://en.wikipedia.org/wiki/Hemolysin#cite_note-pmid20692229-3
- ↑ http://www.sciencedirect.com/science/article/pii/S0005273610002610
- ↑ Cite error: Invalid
<ref>tag; no text was provided for refs namedsod - ↑ 4.0 4.1 4.2 DOI: 10.1016/0092-8674(95)90359-3
- ↑ http://www.mayoclinic.org/diseases-conditions/long-qt-syndrome/basics/definition/con-20025388