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Type: Journal article
Title: AB5 subtilase cytotoxin inactivates the endoplasmic reticulum chaperone BiP
Author: Paton, A.
Beddoe, T.
Thorpe, C.
Whisstock, J.
Wilce, M.
Rossjohn, J.
Talbot, U.
Paton, J.
Citation: Nature, 2006; 443(7111):548-552
Publisher: Nature Publishing Group
Issue Date: 2006
ISSN: 0028-0836
Statement of
Adrienne W. Paton, Travis Beddoe, Cheleste M. Thorpe, James C. Whisstock, Matthew C. J. Wilce, Jamie Rossjohn, Ursula M. Talbot and James C. Paton
Abstract: AB5 toxins are produced by pathogenic bacteria and consist of enzymatic A subunits that corrupt essential eukaryotic cell functions, and pentameric B subunits that mediate uptake into the target cell. AB5 toxins include the Shiga, cholera and pertussis toxins and a recently discovered fourth family, subtilase cytotoxin, which is produced by certain Shiga toxigenic strains of Escherichia coli. Here we show that the extreme cytotoxicity of this toxin for eukaryotic cells is due to a specific single-site cleavage of the essential endoplasmic reticulum chaperone BiP/GRP78. The A subunit is a subtilase-like serine protease; structural studies revealed an unusually deep active-site cleft, which accounts for its exquisite substrate specificity. A single amino-acid substitution in the BiP target site prevented cleavage, and co-expression of this resistant protein protected transfected cells against the toxin. BiP is a master regulator of endoplasmic reticulum function, and its cleavage by subtilase cytotoxin represents a previously unknown trigger for cell death.
Keywords: Vero Cells
Endoplasmic Reticulum
Escherichia coli
Heat-Shock Proteins
Molecular Chaperones
Bacterial Toxins
Binding Sites
Substrate Specificity
Chlorocebus aethiops
Endoplasmic Reticulum Chaperone BiP
Description: Copyright © 2006 Nature Publishing Group
DOI: 10.1038/nature05124
Appears in Collections:Aurora harvest 6
Molecular and Biomedical Science publications

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