Sandbox WWC6
From Proteopedia
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| - | == 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. | ||
| + | ===Pore formation=== | ||
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| - | ===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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===Hemolytic anemia=== | ===Hemolytic 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> | |
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Revision as of 11:12, 13 May 2016
Contents |
Hemolysin
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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Function
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 [4]
Structure
Hemolysins have three structural variations: alpha, beta, and gamma. These hemolysin types are comprised of di-, hepta- or octomeric subunits.[3] The alpha subunit, depicted right, consists of four repeating structures, named I through IV and shown in different colors .
Alpha-hemolysin
Alpha hemolysins cause a partial lysis of red blood cells. The heptameric pore assembles from water-soluble subunits The transmembrane domain of this water-filled pore is primarily comprised of an anti-parallel beta-barrel
Beta-hemolysin
Beta-hemolysins cause a total lysis of red blood cells.
Gamma-hemolysin
Gamma-hemolysin is both hemolytic and leukotoxic.
Pathogenic Microorganisms
Pore-forming toxins have been shown to closely relate to the pathogenicity of the toxin-producing organism [5]
Role in infection
Hemolysin lysis of red blood cells is a marker for many kinds of pathogenic infection characterized by...
Oncology
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. [6][7] It was found that this deletion includes residues 1505-1507 (KPQ).[6] These residues occur in the cytoplasmic linker between domain III and domain IV. [6]
Hemolytic anemia
Hemolytic anemia occurs when lysis of red blood cells occurs are rates faster than they can be replaced by bone marrow. [8]
