6DKK

Structure of BoNT

6DKK の概要

• エントリーDOI: 10.2210/pdb6dkk/pdb
• 分子名称: Botulinum neurotoxin type A, PHOSPHATE ION (3 entities in total)
• 機能のキーワード: protein translocation, botulinum neurotoxin, toxin
• 由来する生物種: Clostridium botulinum A str. ATCC 19397
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 75102.44

構造登録者

Lam, K.,Jin, R. (登録日: 2018-05-29, 公開日: 2018-12-26, 最終更新日: 2023-10-11)

主引用文献

Lam, K.H.,Guo, Z.,Krez, N.,Matsui, T.,Perry, K.,Weisemann, J.,Rummel, A.,Bowen, M.E.,Jin, R.
A viral-fusion-peptide-like molecular switch drives membrane insertion of botulinum neurotoxin A1.
Nat Commun, 9:5367-5367, 2018

PubMed Abstract: Botulinum neurotoxin (BoNT) delivers its protease domain across the vesicle membrane to enter the neuronal cytosol upon vesicle acidification. This process is mediated by its translocation domain (H), but the molecular mechanism underlying membrane insertion of H remains poorly understood. Here, we report two crystal structures of BoNT/A1 H that reveal a novel molecular switch (termed BoNT-switch) in H, where buried α-helices transform into surface-exposed hydrophobic β-hairpins triggered by acidic pH. Locking the BoNT-switch by disulfide trapping inhibited the association of H with anionic liposomes, blocked channel formation by H, and reduced the neurotoxicity of BoNT/A1 by up to ~180-fold. Single particle counting studies showed that an acidic environment tends to promote BoNT/A1 self-association on liposomes, which is partly regulated by the BoNT-switch. These findings suggest that the BoNT-switch flips out upon exposure to the acidic endosomal pH, which enables membrane insertion of H that subsequently leads to LC delivery.

PubMed: 30560862
DOI: 10.1038/s41467-018-07789-4

実験手法

X-RAY DIFFRACTION (2.7 Å)