THE 2.4 ANGSTROM CRYSTAL-STRUCTURE OF CHOLERA-TOXIN-B SUBUNIT PENTAMER - CHOLERAGENOID

Cholera toxin, a heterohexameric AB(5) enterotoxin released by Vibrio cholera, induces a profuse secretory diarrhea in susceptible hosts. Choleragenoid, the B subunit pentamer of cholera toxin, directs the enzymatic A subunit to its target by binding the GM(1) gangliosides exposed on the luminal surface of intestinal epithelial cells. The crystal structure of choleragenoid has been independently solved and refined at 2.4 Angstrom resolution by combining single isomorphous replacement with non-crystallographic symmetry averaging. The structure of the B subunits, and their pentameric arrangement, closely resembles that reported for the intact holotoxin, choleragen, the heat-labile enterotoxin from Escherichia coli, and for a choleragenoid-GM(1) pentasaccharide complex. In the absence of the A subunit the central cavity of the B pentamer is a highly solvated channel. The binding of choleragenoid to the A subunit or to its receptor pentasaccharide modestly affects the local stereochemistry without perceptibly altering the subunit interface. (C) 1995 Academic Press Limited