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Nat Commun. 2013;4:2058. doi: 10.1038/ncomms3058.

Structure of dual receptor binding to botulinum neurotoxin B.

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1
Department of Biochemistry and Biophysics, Stockholm University, Stockholm 10691, Sweden.

Abstract

Botulinum neurotoxins are highly toxic, and bind two receptors to achieve their high affinity and specificity for neurons. Here we present the first structure of a botulinum neurotoxin bound to both its receptors. We determine the 2.3-Å structure of a ternary complex of botulinum neurotoxin type B bound to both its protein receptor synaptotagmin II and its ganglioside receptor GD1a. We show that there is no direct contact between the two receptors, and that the binding affinity towards synaptotagmin II is not influenced by the presence of GD1a. The interactions of botulinum neurotoxin type B with the sialic acid 5 moiety of GD1a are important for the ganglioside selectivity. The structure demonstrates that the protein receptor and the ganglioside receptor occupy nearby but separate binding sites, thus providing two independent anchoring points.

PMID:
23807078
PMCID:
PMC3752466
DOI:
10.1038/ncomms3058
[Indexed for MEDLINE]
Free PMC Article
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