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=Hemolysin= | |||
[[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]. | [[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]. | ||
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== 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. Hemolysins act through disruption of the cell membrane. <ref>http://www.sciencedirect.com/science/article/pii/S0005273610002610</ref> Pore formation<ref name ="sod"/> 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 <ref>http://www.ks.uiuc.edu/Research/hemolysin/<ref>. 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> | |||
==Structure== | ==Structure== | ||
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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 transmembrane domain of this water-filled pore is primarily comprised of an anti-parallel beta-barrel | 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 | ||
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Beta-hemolysins cause a total lysis of red blood cells. | Beta-hemolysins cause a total lysis of red blood cells. | ||
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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. | ||
Revision as of 11:07, 13 May 2016
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 Cite error: Closing </ref> missing for <ref> tag
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 here.
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 Cite error: Closing </ref> missing for <ref> tag
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. [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 anemia
Hyperkalemic period paralysis is caused by the mutations T704M, S906T, A1156T, M1360V, A1448C and/or M1592V. [6] These mutations cause periodic or permanent weakness. [6] Physiologically, this is a gain of function mutation. During rest after exercise, or after eating foods rich in K+, the extracellular K+ increases, which mildly depolarizes the membrane.[6] This causes abnormal Na+ channels to open, and they are unable to inactivate. [6] This sustained depolarization of the membrane causes even more abnormal Na+ channels to open and ultimately this leads to loss of excitability and weakness. [6] This symptom usually appears within the first decade of life and can be aggravated by exercise, cold, potassium loading, fasting or pregnancy. [6] Attacks are usually brief and do not need treatment. [6]
Marker for fungi exposure
Many indoor fungi have been shown to produse both alpha and beta-hemolysins. The treatment of blood samples with
Treatment
References
- ↑ https://en.wikipedia.org/wiki/Hemolysin#cite_note-pmid20692229-3
- ↑ https://www.sciencedirect.com/science/article/pii/S0005273610002610
- ↑ 3.0 3.1 Cite error: Invalid
<ref>tag; no text was provided for refs namedsod - ↑ 4.0 4.1 4.2 doi: https://dx.doi.org/10.1016/0092-8674(95)90359-3
- ↑ https://www.mayoclinic.org/diseases-conditions/long-qt-syndrome/basics/definition/con-20025388
- ↑ 6.0 6.1 6.2 6.3 6.4 6.5 6.6 https://neuromuscular.wustl.edu/mother/activity.html#hrpp
