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https://hdl.handle.net/2440/81172
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dc.contributor.author | Le Nours, J. | - |
dc.contributor.author | Paton, A. | - |
dc.contributor.author | Byres, E. | - |
dc.contributor.author | Troy, S. | - |
dc.contributor.author | Herdman, B. | - |
dc.contributor.author | Johnson, M. | - |
dc.contributor.author | Paton, J. | - |
dc.contributor.author | Rossjohn, J. | - |
dc.contributor.author | Beddoe, T. | - |
dc.date.issued | 2013 | - |
dc.identifier.citation | Journal of Biological Chemistry, 2013; 288(38):27505-27516 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.issn | 1083-351X | - |
dc.identifier.uri | http://hdl.handle.net/2440/81172 | - |
dc.description.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. | - |
dc.description.statementofresponsibility | Jérôme Le Nours, Adrienne W. Paton, Emma Byres, Sally Troy, Brock P. Herdman, Matthew D. Johnson, James C. Paton, Jamie Rossjohn, and Travis Beddoe | - |
dc.language.iso | en | - |
dc.publisher | Amer Soc Biochemistry Molecular Biology Inc | - |
dc.rights | © 2013 by The American Society for Biochemistry and Molecular Biology, Inc. | - |
dc.source.uri | http://dx.doi.org/10.1074/jbc.m113.462622 | - |
dc.subject | Escherichia coli | - |
dc.subject | Disulfides | - |
dc.subject | Subtilisins | - |
dc.subject | Escherichia coli Proteins | - |
dc.subject | Bacterial Toxins | - |
dc.subject | Mutagenesis | - |
dc.subject | Protein Structure, Quaternary | - |
dc.subject | Protein Structure, Tertiary | - |
dc.subject | Structure-Activity Relationship | - |
dc.subject | Protein Transport | - |
dc.title | Structural basis of subtilase cytotoxin SubAB assembly | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1074/jbc.M113.462622 | - |
dc.relation.grant | http://purl.org/au-research/grants/arc/DP1095420 | - |
dc.relation.grant | http://purl.org/au-research/grants/arc/DP120103178 | - |
dc.relation.grant | http://purl.org/au-research/grants/arc/DP1095420 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Paton, J. [0000-0001-9807-5278] | - |
Appears in Collections: | Aurora harvest 4 Molecular and Biomedical Science publications |
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