Structural Basis for the Activation of Cholera Toxin by Human ARF6-GTP -- O'Neal et al. 309 (5737): 1093 -- Science:
The Vibrio cholerae bacterium causes cholera, a serious diarrheal disease that claims thousands of victims in third-world, war-torn, and disaster-stricken nations each year (1). V. cholerae secretes its major virulence factor, cholera toxin (CT), when colonizing the mucosa of the human small intestine. CT is composed of a globular A subunit and a pentamer of B subunits (2, 3). Heat-labile enterotoxin (LT) produced by enterotoxigenic Escherichia coli, which is responsible for hundreds of thousands of children's deaths from diarrheal diseases annually (4), shares more than 80% sequence identity with CT. In both toxins, proteolytic cleavage of the A subunit and reduction of the Cys187-Cys199 disulfide bond covalently separate the A1 and A2 domains, formed by residues 1 to 192 and 193 to 240, respectively (5). A1 is solely responsible for the toxin's enzymatic activity; however, in vivo delivery of the A1 enzyme to its target requires the nonenzymatic B pentamer and A2 peptide, which testifies to an extensive coevolution of the diarrheal pathogens with their human hosts (6, 7).
Co-evolution and common descent explain why we get sick.