The 2.4 Å Crystal Structure of Cholera Toxin B Subunit Pentamer: Choleragenoid

• Published in: Journal of molecular biology 1995-08, Vol.251 (4), p.550-562
• Main Authors: Zhang, Rong-Guang, Westbrook, Mary L., Westbrook, Edwin M., Scott, David L., Otwinowski, Zbyszek, Maulik, Prakas R., Reed, Robert A., Shipley, Graham G.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Binding Sites; cholera toxin; Cholera Toxin - chemistry; Cholera Toxin - metabolism; choleragenoid; crystal structure; Crystallography, X-Ray; enterotoxins; G(M1) Ganglioside - metabolism; gangliosides; Molecular Sequence Data; Protein Conformation; Protein Structure, Secondary
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1006/jmbi.1995.0455

Cholera toxin, a heterohexameric AB 5enterotoxin released by Vibrio choleraeinduces 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 1gangliosides exposed on the luminal surface of intestinal epithelial cells. The crystal structure of choleragenoid has been independently solved and refined at 2.4 Å 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 1pentasaccharide 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.