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2nm1
From Proteopedia
| 2nm1, resolution 2.15Å () | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Gene: | botB (Clostridium botulinum) | ||||||||
| Activity: | Bontoxilysin, with EC number 3.4.24.69 | ||||||||
| Related: | 1f31, 1z0h | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Structure of BoNT/B in complex with its protein receptor
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.
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
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
2nm1 is a 2 chain structure with sequence from Clostridium botulinum and Rattus norvegicus. Full crystallographic information is available from OCA.
Reference
- Jin R, Rummel A, Binz T, Brunger AT. Botulinum neurotoxin B recognizes its protein receptor with high affinity and specificity. Nature. 2006 Dec 21;444(7122):1092-5. Epub 2006 Dec 13. PMID:17167421 doi:10.1038/nature05387
- Swaminathan S, Eswaramoorthy S. Structural analysis of the catalytic and binding sites of Clostridium botulinum neurotoxin B. Nat Struct Biol. 2000 Aug;7(8):693-9. PMID:10932256
- Jayaraman S, Eswaramoorthy S, Ahmed SA, Smith LA, Swaminathan S. N-terminal helix reorients in recombinant C-fragment of Clostridium botulinum type B. Biochem Biophys Res Commun. 2005 Apr 29;330(1):97-103. PMID:15781237 doi:10.1016/j.bbrc.2005.02.123
