2nm1
From Proteopedia
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Structure of BoNT/B in complex with its protein receptor
Overview
Botulinum neurotoxins (BoNTs) are produced by Clostridium botulinum and, cause the neuroparalytic syndrome of botulism. With a lethal dose of 1 ng, kg(-1), they pose a biological hazard to humans and a serious potential, bioweapon threat. BoNTs bind with high specificity at neuromuscular, junctions and they impair exocytosis of synaptic vesicles containing, acetylcholine through specific proteolysis of SNAREs (soluble, N-ethylmaleimide-sensitive fusion protein attachment protein receptors), which constitute part of the synaptic vesicle fusion machinery. The, molecular details of the toxin-cell recognition have been elusive. Here we, report the structure of a BoNT in complex with its protein receptor: the, receptor-binding domain of botulinum neurotoxin serotype B (BoNT/B) bound, to the luminal domain of synaptotagmin II, determined at 2.15 A, resolution. On binding, a helix is induced in the luminal domain which, binds to a saddle-shaped crevice on a distal tip of BoNT/B. This crevice, is adjacent to the non-overlapping ganglioside-binding site of BoNT/B., Synaptotagmin II interacts with BoNT/B with nanomolar affinity, at both, neutral and acidic endosomal pH. Biochemical and neuronal ex vivo studies, of structure-based mutations indicate high specificity and affinity of the, interaction, and high selectivity of BoNT/B among synaptotagmin I and II, isoforms. Synergistic binding of both synaptotagmin and ganglioside, imposes geometric restrictions on the initiation of BoNT/B translocation, after endocytosis. Our results provide the basis for the rational, development of preventive vaccines or inhibitors against these, neurotoxins.
About this Structure
2NM1 is a Single protein structure of sequence from Clostridium botulinum and Rattus norvegicus. Active as Bontoxilysin, with EC number 3.4.24.69 Full crystallographic information is available from OCA.
Reference
Botulinum neurotoxin B recognizes its protein receptor with high affinity and specificity., Jin R, Rummel A, Binz T, Brunger AT, Nature. 2006 Dec 21;444(7122):1092-5. Epub 2006 Dec 13. PMID:17167421
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