Download MendeleyStructural basis for the activation of cholera toxin by human ARF6-GTP.
O'Neal, C.J., Jobling, M.G., Holmes, R.K., Hol, W.G.(2005) Science 309: 1093-1096
- PubMed: 16099990
- DOI: https://doi.org/10.1126/science.1113398
- Primary Citation of Related Structures:
2A5D, 2A5F, 2A5G - 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.
Organizational Affiliation:
Department of Chemistry, University of Washington, Seattle, WA 98195, USA.
