6MHJ
Structure of BoNT mutant
Summary for 6MHJ
| Entry DOI | 10.2210/pdb6mhj/pdb |
| Descriptor | Botulinum neurotoxin type A, PHOSPHATE ION (2 entities in total) |
| Functional Keywords | protein translocation, botulinum neurotoxin, toxin |
| Biological source | Clostridium botulinum A str. ATCC 19397 |
| Total number of polymer chains | 1 |
| Total formula weight | 38340.42 |
| Authors | |
| Primary citation | 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 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: 30560862DOI: 10.1038/s41467-018-07789-4 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.019 Å) |
Structure validation
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