title: Crystal structure of the cell-binding B oligomer of verotoxin-1 from E. coli.
abstract: The Shiga toxin family, a group of cytotoxins associated with diarrhoeal diseases and the haemolytic uraemic syndrome, includes Shiga toxin from Shigella dysenteriae type 1 and verotoxins produced by enteropathogenic Escherichia coli. The family belongs to the A-B class of bacterial toxins, which includes the cholera toxin family, pertussis and diphtheria toxins. These toxins all have bipartite structures consisting of an enzymatic A subunit associated with a B oligomer which binds to specific cell-surface receptors, but their amino-acid sequences and pathogenic mechanisms differ. We have determined the crystal structure of the B oligomer of verotoxin-1 from E. coli. The structure unexpectedly resembles that of the B oligomer of the cholera toxin-like heat-labile enterotoxin from E. coli, despite the absence of detectable sequence similarity between these two proteins. This result implies a distant evolutionary relationship between the Shiga toxin and cholera toxin families. We suggest that the cell surface receptor-binding site lies in a cleft between adjacent subunits of the B pentamer, providing a potential target for drugs and vaccines to prevent toxin binding and effect.
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, University of Alberta, Edmonton, Canada.
authors.forename: P E
authors.initials: PE
authors.lastname: Stein
authors.forename: A
authors.initials: A
authors.lastname: Boodhoo
authors.forename: G J
authors.initials: GJ
authors.lastname: Tyrrell
authors.forename: J L
authors.initials: JL
authors.lastname: Brunton
authors.forename: R J
authors.initials: RJ
authors.lastname: Read
mesh_terms: D001427:Bacterial Toxins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D050260:Carbohydrate Metabolism; D003460:Crystallization; D004926:Escherichia coli / Q000737:chemistry*; D046911:Macromolecular Substances; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D022622:Shiga Toxin 1; D012984:Software; D014961:X-Ray Diffraction
chemical_list: D001427:Bacterial Toxins; D046911:Macromolecular Substances; D022622:Shiga Toxin 1