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Originally published In Press as doi:10.1074/jbc.M103285200 on June 19, 2001

J. Biol. Chem., Vol. 276, Issue 34, 32274-32281, August 24, 2001
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The Crystal Structure of Tetanus Toxin Hc Fragment Complexed with a Synthetic GT1b Analogue Suggests Cross-linking between Ganglioside Receptors and the Toxin*

Constantina FotinouDagger , Paul EmsleyDagger , Isobel BlackDagger , Hiromune Ando§, Hideharu Ishida§, Makoto Kiso§, Katharine A. Sinha, Neil F. Fairweather, and Neil W. IsaacsDagger ||

From the Dagger  Department of Chemistry, University of Glasgow, Glasgow, G12 8QQ, Scotland, the § Department of Applied Bio-organic Chemistry, Gifu University, Gifu 501-1193, Japan, and the  Department of Biochemistry, Imperial College of Science and Technology Medicine, London SW7 2AZ, United Kingdom

Tetanus toxin, a member of the family of Clostridial neurotoxins, is one of the most potent toxins known. The crystal structure of the complex of the COOH-terminal fragment of the heavy chain with an analogue of its ganglioside receptor, GT1b, provides the first direct identification and characterization of the ganglioside-binding sites. The ganglioside induces cross-linking by binding to two distinct sites on the Hc molecule. The structure sheds new light on the binding of Clostridial neurotoxins to receptors on neuronal cells and provides important information relevant to the design of anti-tetanus and anti-botulism therapeutic agents.


* This work was supported by Grants 053570 and 051615 from The Wellcome Trust.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The atomic coordinates and the structure factors (code 1fv2 and 1fv3) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

|| To whom correspondence should be addressed. Tel.: 44-141-3305954; Fax: 44-141-3304888; E-mail: neil@chem.gla.ac.uk.


Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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