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

Article Details

Citation

O'Neal CJ, Jobling MG, Holmes RK, Hol WG

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

Science. 2005 Aug 12;309(5737):1093-6.

PubMed ID
16099990 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
ADP-ribosylation factor 6P62330Details