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https://hdl.handle.net/2440/81172
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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 1083-351X |
Statement of Responsibility: | 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 Disulfides Subtilisins Escherichia coli Proteins Bacterial Toxins Mutagenesis 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: | http://purl.org/au-research/grants/arc/DP1095420 http://purl.org/au-research/grants/arc/DP120103178 http://purl.org/au-research/grants/arc/DP1095420 |
Published version: | http://dx.doi.org/10.1074/jbc.m113.462622 |
Appears in Collections: | Aurora harvest 4 Molecular and Biomedical Science publications |
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