Structural Basis for the Activation of Cholera Toxin by Human ARF6-GTP
- 12 August 2005
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 309 (5737), 1093-1096
- https://doi.org/10.1126/science.1113398
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 G Sα , 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.Keywords
This publication has 33 references indexed in Scilit:
- Structural Principles for the Multispecificity of Small GTP-Binding ProteinsBiochemistry, 2004
- Crystal Structures of an Intrinsically Active Cholera Toxin Mutant Yield Insight into the Toxin Activation Mechanism,Biochemistry, 2004
- The Crystal Structure of C3stau2 from Staphylococcus aureus and Its Complex with NADJournal of Biological Chemistry, 2003
- NAD Binding Induces Conformational Changes in Rho ADP-ribosylating Clostridium botulinum C3 ExoenzymePublished by Elsevier BV ,2002
- Biological and Biochemical Characterization of Variant A Subunits of Cholera Toxin Constructed by Site-Directed MutagenesisJournal of Bacteriology, 2001
- Crystal structure and novel recognition motif of Rho ADP-ribosylating C3 exoenzyme from Clostridium botulinum: structural insights for recognition specificity and catalysisJournal of Molecular Biology, 2001
- Pathogenicity Islands and the Evolution of MicrobesAnnual Review of Microbiology, 2000
- The Three-dimensional Crystal Structure of Cholera ToxinJournal of Molecular Biology, 1995
- Activation of Escherichia coli heat-labile enterotoxins by native and recombinant adenosine diphosphate-ribosylation factors, 20-kD guanine nucleotide-binding proteins.JCI Insight, 1991
- Mechanism of cholera toxin activation by a guanine nucleotide-dependent 19 kDa proteinBiochimica et Biophysica Acta (BBA) - General Subjects, 1990