Abstract
Clostridium botulinum neurotoxins (BoNTs) cause flaccid paralysis through inhibition of acetylcholine release from motor neurons; however, at tiny doses, this property is exploited for use as a therapeutic. Each member of the BoNT family of proteins consists of three distinct domains: a binding domain that targets neuronal cell membranes (HC), a translocation domain (HN) and a catalytic domain (LC). Here, we present high-resolution crystal structures of the binding domains of BoNT subtypes/A5 (HC/A5) and/A6 (HC/A6). These structures show that the core fold identified in other subtypes is maintained, but with subtle differences at the expected receptor-binding sites.
Original language | English |
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Pages (from-to) | 1474-1481 |
Number of pages | 8 |
Journal | FEBS Open Bio |
Volume | 10 |
Issue number | 8 |
Early online date | 23 Jul 2020 |
DOIs | |
Publication status | Published - 1 Aug 2020 |
Funding
We thank Diamond Light Source (UK) for the use of beamlines IO3 and IO4-1 (proposal mx17212). J.R.D. was supported by a joint postgraduate studentship between University of Bath (UK) and Ipsen Bioinnovation Limited.
Keywords
- binding domain structure
- botulinum neurotoxin
- Clostridium botulinum
- subtypes
- X-ray crystallography
ASJC Scopus subject areas
- General Biochemistry,Genetics and Molecular Biology