Structure of the Shiga-like Toxin I B-Pentamer Complexed with an Analogue of Its Receptor Gb3

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, globo...

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Veröffentlicht in:Biochemistry (Easton) 1998-02, Vol.37 (7), p.1777-1788
Hauptverfasser: Ling, Hong, Boodhoo, Amechand, Hazes, Bart, Cummings, Maxwell D, Armstrong, Glen D, Brunton, James L, Read, Randy J
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Sprache:eng
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Zusammenfassung: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 Å 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.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi971806n