Abstract
The tetanus neurotoxin (TeNT) is a highly potent toxin produced by Clostridium tetani that inhibits neurotransmission of inhibitory interneurons, causing spastic paralysis in the tetanus disease. TeNT differs from the other clostridial neurotoxins by its unique ability to target the central nervous system by retrograde axonal transport. The crystal structure of the tetanus toxin reveals a “closed” domain arrangement stabilised by two disulphide bridges, and the molecular details of the toxin's interaction with its polysaccharide receptor. An integrative analysis combining X-ray crystallography, solution scattering and single particle electron cryo-microscopy reveals pH-mediated domain rearrangements that may give TeNT the ability to adapt to the multiple environments encountered during intoxication, and facilitate binding to distinct receptors.
| Original language | English |
|---|---|
| Pages (from-to) | 1306-1317 |
| Number of pages | 12 |
| Journal | EMBO Reports |
| Volume | 18 |
| Issue number | 8 |
| Early online date | 23 Jun 2017 |
| DOIs | |
| Publication status | Published - 23 Jun 2017 |
Funding
We thank the scientists at stations I04-1 and B21 of Diamond Light Source, Didcot, Oxfordshire (UK) for their support during X-ray diffraction and SAXS data collection. We are grateful to Michael Lerche for his help in SAXS data collection and analysis. This work was supported by grants from the Swedish Research Council (2010-5200, 2014-5667), the Wenner-Gren Foundations and the Swedish Cancer Society to P.S. The cryo-EM data were collected at the UK National Electron Bio-imaging Centre (eBIC), proposal #EM14185-2 to Alexey Amunts, funded by the Wellcome Trust, MRC and BBSRC; and at the Swedish National Cryo-EM Facility funded by the Knut and Alice Wallenberg, Family Erling Persson Foundation and SciLifeLab Stockholm University. Computer resources were provided by Alexey Amunts.
Keywords
- clostridial toxin
- tentoxilysin
- tetanospasmin
- tetanus neurotoxin
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Genetics