Loading
PDBj
MenuPDBj@FacebookPDBj@TwitterPDBj@YouTubewwPDB FoundationwwPDB
RCSB PDBPDBeBMRBAdv. SearchSearch help

6DKK

Structure of BoNT

Summary for 6DKK
Entry DOI10.2210/pdb6dkk/pdb
DescriptorBotulinum neurotoxin type A, PHOSPHATE ION (3 entities in total)
Functional Keywordsprotein translocation, botulinum neurotoxin, toxin
Biological sourceClostridium botulinum A str. ATCC 19397
Total number of polymer chains2
Total formula weight75102.44
Authors
Lam, K.,Jin, R. (deposition date: 2018-05-29, release date: 2018-12-26, Last modification date: 2023-10-11)
Primary citationLam, 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
Cited by
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
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.7 Å)
Structure validation

226707

数据于2024-10-30公开中

PDB statisticsPDBj update infoContact PDBjnumon