Sandbox WWC6
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 K+ ions 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. 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.[2] Each hemolysin pore is composed of three subunits: the alpha subunit, which is the transmembrane ion channel, and two beta subunits that modulate channel gating and regulate the channel expression in the membrane. [3] [4] The alpha subunit is able to function independently of the beta subunit. [3]
Hemolysins act through disruption of the cell membrane. Two main functions destroy phospholipid membranes: pore formation and phosphilipid hydrosysis. [5] Pore formation, the most common mechanism of hemolysin cell [4] This information was first discovered by Hodgkin and Huxley in 1952. [6] For more information on the role of sodium channels in electrical signaling, click here.
StructureStructure
Hemolysins have three structural variations: alpha, beta, and gamma. These hemolysin types are comprised of di-, hepta- or octomeric subunits.[4] The alpha subunit, depicted right, consists of four repeating structures, named I through IV and shown in different colors . [7] These structures consist of six transmembrane alpha helices named S1 through S6. [7] Interestingly, each repeating subunit resembles a bacterial K+ channel. [7] These subunits fold together to form a central pore, and this complete structure resembles a bacterial Ca2+ channel. [7]
Alpha-hemolysinAlpha-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-hemolysinBeta-hemolysin
Beta-hemolysins cause a total lysis of red blood cells.
Gamma-hemolysinGamma-hemolysin
Gamma-hemolysin is both hemolytic and leukotoxic.
Pathogenic MicroorganismsPathogenic 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
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. [8][9] It was found that this deletion includes residues 1505-1507 (KPQ).[8] These residues occur in the cytoplasmic linker between domain III and domain IV. [8]
Hemolytic anemiaHemolytic anemia
Hyperkalemic period paralysis is caused by the mutations T704M, S906T, A1156T, M1360V, A1448C and/or M1592V. [10] These mutations cause periodic or permanent weakness. [10] 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.[10] This causes abnormal Na+ channels to open, and they are unable to inactivate. [10] This sustained depolarization of the membrane causes even more abnormal Na+ channels to open and ultimately this leads to loss of excitability and weakness. [10] This symptom usually appears within the first decade of life and can be aggravated by exercise, cold, potassium loading, fasting or pregnancy. [10] Attacks are usually brief and do not need treatment. [10]
ReferencesReferences
- ↑ https://en.wikipedia.org/wiki/Hemolysin#cite_note-pmid20692229-3
- ↑ http://www.nhlbi.nih.gov/health/health-topics/topics/ha/
- ↑ 3.0 3.1 Isom LL. Sodium channel beta subunits: anything but auxiliary. Neuroscientist. 2001 Feb;7(1):42-54. PMID:11486343
- ↑ 4.0 4.1 4.2 Cite error: Invalid
<ref>tag; no text was provided for refs namedsod - ↑ http://www.sciencedirect.com/science/article/pii/S0005273610002610
- ↑ https://en.wikipedia.org/wiki/Hodgkin%E2%80%93Huxley_model
- ↑ 7.0 7.1 7.2 7.3 Marban E, Yamagishi T, Tomaselli GF. Structure and function of voltage-gated sodium channels. J Physiol. 1998 May 1;508 ( Pt 3):647-57. doi: 10.1111/j.1469-7793.1998.647bp.x. PMID:9518722 doi:http://dx.doi.org/10.1111/j.1469-7793.1998.647bp.x
- ↑ 8.0 8.1 8.2 DOI: 10.1016/0092-8674(95)90359-3
- ↑ http://www.mayoclinic.org/diseases-conditions/long-qt-syndrome/basics/definition/con-20025388
- ↑ 10.0 10.1 10.2 10.3 10.4 10.5 10.6 http://neuromuscular.wustl.edu/mother/activity.html#hrpp