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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
The Crystal Structure of Tetanus Toxin Hc Fragment
Complexed with a Synthetic GT1b Analogue Suggests Cross-linking between
Ganglioside Receptors and the Toxin*
Constantina
Fotinou ,
Paul
Emsley ,
Isobel
Black ,
Hiromune
Ando§,
Hideharu
Ishida§,
Makoto
Kiso§,
Katharine A.
Sinha¶,
Neil F.
Fairweather¶, and
Neil W.
Isaacs
From the 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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Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.
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