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EcxAB is a founding member of a new family of metalloprotease AB5 toxins with a hybrid cholera-like B subunit

Ng, Natasha M., Littler, Dene R., Paton, Adrienne W., Le Nours, Jérôme, Rossjohn, Jamie ORCID: https://orcid.org/0000-0002-2020-7522, Paton, James C. and Beddoe, Travis 2013. EcxAB is a founding member of a new family of metalloprotease AB5 toxins with a hybrid cholera-like B subunit. Structure 21 (11) , pp. 2003-2013. 10.1016/j.str.2013.08.024

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Abstract

AB5 toxins are composed of an enzymatic A subunit that disrupts cellular function associated with a pentameric B subunit required for host cell invasion. EcxAB is an AB5 toxin isolated from clinical strains of Escherichia coli classified as part of the cholera family due to B subunit homology. Cholera-group toxins have catalytic ADP-ribosyltransferases as their A subunits, so it was surprising that EcxA did not. We confirmed that EcxAB self-associates as a functional toxin and obtained its structure. EcxAB is a prototypical member of a hybrid AB5 toxin family containing metzincin-type metalloproteases as their active A subunit paired to a cholera-like B subunit. Furthermore, EcxA is distinct from previously characterized proteases and thus founds an AB5-associated metzincin family that we term the toxilysins. EcxAB provides the first observation of conserved B subunit usage across different AB5 toxin families and provides evidence that the intersubunit interface of these toxins is far more permissive than previously supposed.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
R Medicine > RZ Other systems of medicine
Uncontrolled Keywords: Animals; Binding Sites; Catalytic Domain; Cercopithecus aethiops; CHO Cells; Cricetinae; Cricetulus; Crystallography X-Ray; Escherichia coli; Escherichia coli Proteins; Hydrogen Bonding; Metalloproteases; Models Molecular; Polysaccharides; Protein Structure Quaternary; Protein Structure Secondary; Protein Subunits; Vero Cells
Publisher: Elsevier
ISSN: 0969-2126
Last Modified: 28 Oct 2022 09:41
URI: https://orca.cardiff.ac.uk/id/eprint/75369

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