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2nm1
From Proteopedia
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[[Image:2nm1.gif|left|200px]] | [[Image:2nm1.gif|left|200px]] | ||
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'''Structure of BoNT/B in complex with its protein receptor''' | '''Structure of BoNT/B in complex with its protein receptor''' | ||
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[[Category: Jin, R.]] | [[Category: Jin, R.]] | ||
[[Category: Rummel, A.]] | [[Category: Rummel, A.]] | ||
| - | [[Category: | + | [[Category: Botulism]] |
| - | [[Category: | + | [[Category: Neurotransmission]] |
| - | [[Category: | + | [[Category: Synaptotagmin]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 09:37:45 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 06:37, 4 May 2008
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. 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 Page seeded by OCA on Sun May 4 09:37:45 2008
