Abstract
Botulinum neurotoxins (BoNTs) are the most potent toxins known. So far, eight serotypes have been identified that all act as zinc-dependent endopeptidases targeting SNARE proteins and inhibiting the release of neurotransmitters. Recently, the first botulinum toxin-like protein was identified outside the Clostridial genus, designated BoNT/Wo in the genome of Weissella oryzae. Here, we report the 1.6 Å X-ray crystal structure of the light chain of BoNT/Wo (LC/Wo). LC/Wo presents the core fold common to BoNTs but has an unusually wide, open and negatively charged catalytic pocket, with an additional Ca2+ ion besides the zinc ion and a unique ß-hairpin motif. The structural information will help establish the substrate profile of BoNT/Wo and help our understanding of how BoNT evolved.
| Original language | English |
|---|---|
| Pages (from-to) | 1403-1410 |
| Number of pages | 8 |
| Journal | FEBS Letters |
| Volume | 593 |
| Issue number | 12 |
| Early online date | 31 May 2019 |
| DOIs | |
| Publication status | Published - 1 Jun 2019 |
Funding
We thank the scientists at stations I03 of the Diamond Light Source (UK, allocation MX15806) for their support during X-ray data collection. We also thank PSF for protein production. This study was supported by the Swedish Research Council (2018-03406) and the Swedish Cancer Society (to PS), by National Institute of Health (NIH) grants (R01NS080833, R01AI132387, R01AI139087, and R21NS106159 to M.D.). M.D. holds the Investigator in the Pathogenesis of Infectious Disease award from the Burroughs Welcome Fund.
Keywords
- botulinum neurotoxin
- Weissella oryzae
- X-ray crystallography
- zinc endopeptidase
ASJC Scopus subject areas
- Biophysics
- Structural Biology
- Biochemistry
- Molecular Biology
- Genetics
- Cell Biology