2NM1

Structure of BoNT/B in complex with its protein receptor

2NM1 の概要

• エントリーDOI: 10.2210/pdb2nm1/pdb
• 関連するPDBエントリー: 1F31 1Z0H
• 分子名称: Botulinum neurotoxin type B, Synaptotagmin-2 (3 entities in total)
• 機能のキーワード: neurotransmission, botulism, synaptotagmin, toxin, hydrolase
• 由来する生物種: Clostridium botulinum; 詳細
• 細胞内の位置: Botulinum neurotoxin B light chain: Secreted. Botulinum neurotoxin B heavy chain: Secreted: P10844
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 54525.44

構造登録者

Jin, R.,Rummel, A.,Binz, T.,Brunger, A.T. (登録日: 2006-10-20, 公開日: 2006-12-19, 最終更新日: 2023-08-30)

主引用文献

Jin, R.,Rummel, A.,Binz, T.,Brunger, A.T.
Botulinum neurotoxin B recognizes its protein receptor with high affinity and specificity.
Nature, 444:1092-1095, 2006

PubMed Abstract: 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.

PubMed: 17167421
DOI: 10.1038/nature05387

実験手法

X-RAY DIFFRACTION (2.15 Å)