Publication Abstract from PubMed
Shiga-like toxin I (SLT-I) is a virulence factor of Escherichia coli strains that cause disease in humans. Like other members of the Shiga toxin family, it consists of an enzymatic (A) subunit and five copies of a binding subunit (the B-pentamer). The B-pentamer binds to a specific glycolipid, globotriaosylceramide (Gb3), on the surface of target cells and thereby plays a crucial role in the entry of the toxin. Here we present the crystal structure at 2.8 A resolution of the SLT-I B-pentamer complexed with an analogue of the Gb3 trisaccharide. The structure reveals a surprising density of binding sites, with three trisaccharide molecules bound to each B-subunit monomer of 69 residues. All 15 trisaccharides bind to one side of the B-pentamer, providing further evidence that this side faces the cell membrane. The structural model is consistent with data from site-directed mutagenesis and binding of carbohydrate analogues, and allows the rational design of therapeutic Gb3 analogues that block the attachment of toxin to cells.
Structure of the shiga-like toxin I B-pentamer complexed with an analogue of its receptor Gb3.,Ling H, Boodhoo A, Hazes B, Cummings MD, Armstrong GD, Brunton JL, Read RJ Biochemistry. 1998 Feb 17;37(7):1777-88. PMID:9485303[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
