2nm1: Difference between revisions

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[[Image:2nm1.gif|left|200px]]
{{Seed}}
[[Image:2nm1.png|left|200px]]


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{{STRUCTURE_2nm1|  PDB=2nm1  |  SCENE=  }}  
{{STRUCTURE_2nm1|  PDB=2nm1  |  SCENE=  }}  


'''Structure of BoNT/B in complex with its protein receptor'''
===Structure of BoNT/B in complex with its protein receptor===




==Overview==
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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.
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{{ABSTRACT_PUBMED_17167421}}


==About this Structure==
==About this Structure==
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==Reference==
==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:[http://www.ncbi.nlm.nih.gov/pubmed/17167421 17167421]
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:[http://www.ncbi.nlm.nih.gov/pubmed/17167421 17167421]
Structural analysis of the catalytic and binding sites of Clostridium botulinum neurotoxin B., Swaminathan S, Eswaramoorthy S, Nat Struct Biol. 2000 Aug;7(8):693-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10932256 10932256]
N-terminal helix reorients in recombinant C-fragment of Clostridium botulinum type B., Jayaraman S, Eswaramoorthy S, Ahmed SA, Smith LA, Swaminathan S, Biochem Biophys Res Commun. 2005 Apr 29;330(1):97-103. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15781237 15781237]
[[Category: Bontoxilysin]]
[[Category: Bontoxilysin]]
[[Category: Clostridium botulinum]]
[[Category: Clostridium botulinum]]
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[[Category: Neurotransmission]]
[[Category: Neurotransmission]]
[[Category: Synaptotagmin]]
[[Category: Synaptotagmin]]
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