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|Web of Science®
|Structural basis of subtilase cytotoxin SubAB assembly
|Le Nours, J.
|Journal of Biological Chemistry, 2013; 288(38):27505-27516
|Amer Soc Biochemistry Molecular Biology Inc
|Jérôme Le Nours, Adrienne W. Paton, Emma Byres, Sally Troy, Brock P. Herdman, Matthew D. Johnson, James C. Paton, Jamie Rossjohn, and Travis Beddoe
|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.
Escherichia coli Proteins
Protein Structure, Quaternary
Protein Structure, Tertiary
|© 2013 by The American Society for Biochemistry and Molecular Biology, Inc.
|Appears in Collections:
|Aurora harvest 4
Molecular and Biomedical Science publications
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