Please use this identifier to cite or link to this item:
Scopus Web of Science® Altmetric
Type: Journal article
Title: Structural basis of subtilase cytotoxin SubAB assembly
Author: Le Nours, J.
Paton, A.
Byres, E.
Troy, S.
Herdman, B.
Johnson, M.
Paton, J.
Rossjohn, J.
Beddoe, T.
Citation: Journal of Biological Chemistry, 2013; 288(38):27505-27516
Publisher: Amer Soc Biochemistry Molecular Biology Inc
Issue Date: 2013
ISSN: 0021-9258
Statement of
Jérôme Le Nours, Adrienne W. Paton, Emma Byres, Sally Troy, Brock P. Herdman, Matthew D. Johnson, James C. Paton, Jamie Rossjohn, and Travis Beddoe
Abstract: Pathogenic strains of Escherichia coli produce a number of toxins that belong to the AB5 toxin family, which comprise a catalytic A-subunit that induces cellular dysfunction and a B-pentamer that recognizes host glycans. Although the molecular actions of many of the individual subunits of AB5 toxins are well understood, how they self-associate and the effect of this association on cytotoxicity are poorly understood. Here we have solved the structure of the holo-SubAB toxin that, in contrast to other AB5 toxins whose molecular targets are located in the cytosol, cleaves the endoplasmic reticulum chaperone BiP. SubA interacts with SubB in a similar manner to other AB5 toxins via the A2 helix and a conserved disulfide bond that joins the A1 domain with the A2 helix. The structure revealed that the active site of SubA is not occluded by the B-pentamer, and the B-pentamer does not enhance or inhibit the activity of SubA. Structure-based sequence comparisons with other AB5 toxin family members, combined with extensive mutagenesis studies on SubB, show how the hydrophobic patch on top of the B-pentamer plays a dominant role in binding the A-subunit. The structure of SubAB and the accompanying functional characterization of various mutants of SubAB provide a framework for understanding the important role of the B-pentamer in the assembly and the intracellular trafficking of this AB5 toxin.
Keywords: Escherichia coli
Escherichia coli Proteins
Bacterial Toxins
Protein Structure, Quaternary
Protein Structure, Tertiary
Structure-Activity Relationship
Protein Transport
Rights: © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.
DOI: 10.1074/jbc.M113.462622
Grant ID:
Published version:
Appears in Collections:Aurora harvest 4
Molecular and Biomedical Science publications

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.