1g8z
From Proteopedia
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'''HIS57ALA MUTANT OF CHOLERA TOXIN B-PENATMER''' | '''HIS57ALA MUTANT OF CHOLERA TOXIN B-PENATMER''' | ||
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[[Category: Merritt, E A.]] | [[Category: Merritt, E A.]] | ||
[[Category: Rodigherio, C.]] | [[Category: Rodigherio, C.]] | ||
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| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 17:17:38 2008'' | |
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Revision as of 14:17, 2 May 2008
HIS57ALA MUTANT OF CHOLERA TOXIN B-PENATMER
Overview
GM1-ganglioside receptor binding by the B subunit of cholera toxin (CtxB) is widely accepted to initiate toxin action by triggering uptake and delivery of the toxin A subunit into cells. More recently, GM1 binding by isolated CtxB, or the related B subunit of Escherichia coli heat-labile enterotoxin (EtxB), has been found to modulate leukocyte function, resulting in the down-regulation of proinflammatory immune responses that cause autoimmune disorders such as rheumatoid arthritis and diabetes. Here, we demonstrate that GM1 binding, contrary to expectation, is not sufficient to initiate toxin action. We report the engineering and crystallographic structure of a mutant cholera toxin, with a His to Ala substitution in the B subunit at position 57. Whereas the mutant retained pentameric stability and high affinity binding to GM1-ganglioside, it had lost its immunomodulatory activity and, when part of the holotoxin complex, exhibited ablated toxicity. The implications of these findings on the mode of action of cholera toxin are discussed.
About this Structure
1G8Z is a Single protein structure of sequence from Vibrio cholerae. Full crystallographic information is available from OCA.
Reference
A mutant cholera toxin B subunit that binds GM1- ganglioside but lacks immunomodulatory or toxic activity., Aman AT, Fraser S, Merritt EA, Rodigherio C, Kenny M, Ahn M, Hol WG, Williams NA, Lencer WI, Hirst TR, Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8536-41. Epub 2001 Jul 10. PMID:11447291 Page seeded by OCA on Fri May 2 17:17:38 2008
