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Structural basis for the activation of cholera toxin by human ARF6-GTP.

Authors
Type
Published Article
Journal
Science
1095-9203
Publisher
American Association for the Advancement of Science (AAAS)
Publication Date
Volume
309
Issue
5737
Pages
1093–1096
Identifiers
PMID: 16099990
Source
Medline
License
Unknown

Abstract

The Vibrio cholerae bacterium causes devastating diarrhea when it infects the human intestine. The key event is adenosine diphosphate (ADP)-ribosylation of the human signaling protein GSalpha, catalyzed by the cholera toxin A1 subunit (CTA1). This reaction is allosterically activated by human ADP-ribosylation factors (ARFs), a family of essential and ubiquitous G proteins. Crystal structures of a CTA1:ARF6-GTP (guanosine triphosphate) complex reveal that binding of the human activator elicits dramatic changes in CTA1 loop regions that allow nicotinamide adenine dinucleotide (NAD+) to bind to the active site. The extensive toxin:ARF-GTP interface surface mimics ARF-GTP recognition of normal cellular protein partners, which suggests that the toxin has evolved to exploit promiscuous binding properties of ARFs.

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