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 |
| + | |PDB= 2nm1 |SIZE=350|CAPTION= <scene name='initialview01'>2nm1</scene>, resolution 2.15Å | ||
| + | |SITE= | ||
| + | |LIGAND= | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Bontoxilysin Bontoxilysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.69 3.4.24.69] | ||
| + | |GENE= botB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1491 Clostridium botulinum]) | ||
| + | }} | ||
| + | |||
| + | '''Structure of BoNT/B in complex with its protein receptor''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2NM1 is a [ | + | 2NM1 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NM1 OCA]. |
==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:// | + | 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] |
[[Category: Bontoxilysin]] | [[Category: Bontoxilysin]] | ||
[[Category: Clostridium botulinum]] | [[Category: Clostridium botulinum]] | ||
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[[Category: synaptotagmin]] | [[Category: synaptotagmin]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:48:10 2008'' |
Revision as of 15:48, 20 March 2008
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| , resolution 2.15Å | |||||||
|---|---|---|---|---|---|---|---|
| Gene: | botB (Clostridium botulinum) | ||||||
| Activity: | Bontoxilysin, with EC number 3.4.24.69 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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
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