Shiga toxin: Difference between revisions
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==Introduction== | ==Introduction== | ||
'''Shiga Toxins''' are a family of [http://en.wikipedia.org/wiki/AB5_toxin AB5] toxins which cause dysentery in humans. They are primarily secreted by Shiga toxin-encoding Escherichia coli (STEC), notably by the 0157:H7 strain.<ref name=Wagner>PMID: 12010491</ref> The stx gene is not endogenous to these strains, but is introduced by environmental prophages of the lambda bacteriophage family and incorporated into the E. Coli genome.<ref name=Wagner>PMID: 12010491</ref> | '''Shiga Toxins''' are a family of [http://en.wikipedia.org/wiki/AB5_toxin AB5] toxins (Stx1 and Stx2) which cause dysentery and hemolytic-uremic syndrome in humans. They are primarily secreted by Shiga toxin-encoding Escherichia coli (STEC), notably by the 0157:H7 strain.<ref name=Wagner>PMID: 12010491</ref> STEC's are one of the major foodborne pathogens, affecting both developed and third-world countries. The stx gene is not endogenous to these strains, but is introduced by environmental prophages of the lambda bacteriophage family and incorporated into the E. Coli genome.<ref name=Wagner>PMID: 12010491</ref> Shiga Toxins are closely related to [[ricin]], which is structurally and mechanistically similar. Shiga toxin acts to inhibit protein synthesis in eukaryotic cells and is the main virulence factor of STEC. | ||
==Structure== | ==Structure== | ||
Revision as of 03:14, 21 October 2011
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IntroductionIntroduction
Shiga Toxins are a family of AB5 toxins (Stx1 and Stx2) which cause dysentery and hemolytic-uremic syndrome in humans. They are primarily secreted by Shiga toxin-encoding Escherichia coli (STEC), notably by the 0157:H7 strain.[1] STEC's are one of the major foodborne pathogens, affecting both developed and third-world countries. The stx gene is not endogenous to these strains, but is introduced by environmental prophages of the lambda bacteriophage family and incorporated into the E. Coli genome.[1] Shiga Toxins are closely related to ricin, which is structurally and mechanistically similar. Shiga toxin acts to inhibit protein synthesis in eukaryotic cells and is the main virulence factor of STEC.
StructureStructure
Shiga Toxin consists consists of an AB5 hexamer.[2] The interacts with the via a and .[2]. The glycosidase active site is located on the A subunit, but is blocked by the B subunit until they are cleaved and an active A subunit is released into the target cell.[2]
FunctionFunction
Shiga Toxin acts as an N-glycosidase, removing an adenine from the 60S ribosomal rRNA of a target cell leading to reduced protein synthesis.[3] The B subunit is necessary for binding to eukaryotic cell surface, where it is then endocytosed and proteolytically cleaved into two active A subunits and a B subunit. On the A subunit are all essential in glycosidic activity.[3]
3D structures3D structures
1dm0 - Stx1
1r4q - Stx2
1r4p - Stx2 bound to ligand
2ga4 - Stx2 with adenine
Mutants
1c48 - Shiga-like toxin B subunit
1cqf - Shiga-like toxin B subunit bound to trisaccharide
1bos - Shiga-like toxin bound to receptor
ReferencesReferences
- ↑ 1.0 1.1 Wagner PL, Livny J, Neely MN, Acheson DW, Friedman DI, Waldor MK. Bacteriophage control of Shiga toxin 1 production and release by Escherichia coli. Mol Microbiol. 2002 May;44(4):957-70. PMID:12010491
- ↑ 2.0 2.1 2.2 Fraser ME, Chernaia MM, Kozlov YV, James MN. Crystal structure of the holotoxin from Shigella dysenteriae at 2.5 A resolution. Nat Struct Biol. 1994 Jan;1(1):59-64. PMID:7656009
- ↑ 3.0 3.1 Di R, Kyu E, Shete V, Saidasan H, Kahn PC, Tumer NE. Identification of amino acids critical for the cytotoxicity of Shiga toxin 1 and 2 in Saccharomyces cerevisiae. Toxicon. 2011 Mar 15;57(4):525-39. Epub 2010 Dec 22. PMID:21184769 doi:10.1016/j.toxicon.2010.12.006