High resolution crystal structures of the receptor-binding domain of Clostridium botulinum neurotoxin serotypes A and FA

Jonathan R Davies; Gavin S Hackett; Sai Man Liu; K Ravi Acharya

doi:10.7717/peerj.4552

High resolution crystal structures of the receptor-binding domain of Clostridium botulinum neurotoxin serotypes A and FA

PeerJ. 2018 Mar 21:6:e4552. doi: 10.7717/peerj.4552. eCollection 2018.

Authors

Jonathan R Davies¹, Gavin S Hackett², Sai Man Liu², K Ravi Acharya¹

Affiliations

¹ Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
² Ipsen Bioinnovation Limited, Abingdon, United Kingdom.

Abstract

The binding specificity of botulinum neurotoxins (BoNTs) is primarily a consequence of their ability to bind to multiple receptors at the same time. BoNTs consist of three distinct domains, a metalloprotease light chain (LC), a translocation domain (H_N) and a receptor-binding domain (H_C). Here we report the crystal structure of H_C/FA, complementing an existing structure through the modelling of a previously unresolved loop which is important for receptor-binding. Our H_C/FA structure also contains a previously unidentified disulphide bond, which we have also observed in one of two crystal forms of H_C/A1. This may have implications for receptor-binding and future recombinant toxin production.

Keywords: Botulinum neurotoxin; Crystal structure; FA hybrid; Receptor binding domain; SV2; Targeted secretion inhibitor.

Grants and funding

K. Ravi Acharya received a Research Fellowship from Ipsen Bioinnovation Limited and Jonathan R. Davies is supported by a joint post-graduate studentship between University of Bath and Ipsen Bioinnovation Limited. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.