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Cholera toxin's harmful handshake COURTESY OF RANDALL HOLMES AND WIM HOL A new study gives a peek at how cholera-causing bacteria trigger devastating bouts of diarrhea that can lead to severe dehydration and, if untreated, death (Science 2005, 309, 1093). Cholera is ca used by infection of the human intestine by Vibrio cholerae. When activated by its human host, the toxin produced by this bacterium catalyzes the transfer of an adenosine diphosphate ribosyl group from the cofactor nicotinamide adenine dinucleotide (NAD+) to the human signaling protein Gsá. This chemical modification triggers a chain of events that result in the intestine being flooded with water and salts, generating the watery diarrhea characteristic of cholera. Wim G. J. Hol and Claire J. O'Neal of the University of Washington, Seattle, and Michael G. Jobling of the University of Colorado Health Sciences Center used X-ray crystallography to probe how a ubiquitous human G protein activates the cholera toxin to catalyze this crucial protein modification. They find that binding of the human G protein (yellow) induces a dramatic conformational change in the toxin (gray) that allows NAD+ (ball-and-stick model) to bind to the toxin's active site (green). The regions thought to bind Gsá are shown in red and brown. |
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