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

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 (HN) and a receptor-binding domain (HC). Here we re...

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Main Authors: Jonathan R. Davies, Gavin S. Hackett, Sai Man Liu, K. Ravi Acharya
Format: Article
Language:English
Published: PeerJ Inc. 2018-03-01
Series:PeerJ
Subjects:
Online Access:https://peerj.com/articles/4552.pdf
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author Jonathan R. Davies
Gavin S. Hackett
Sai Man Liu
K. Ravi Acharya
author_facet Jonathan R. Davies
Gavin S. Hackett
Sai Man Liu
K. Ravi Acharya
author_sort Jonathan R. Davies
collection DOAJ
description 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 (HN) and a receptor-binding domain (HC). Here we report the crystal structure of HC/FA, complementing an existing structure through the modelling of a previously unresolved loop which is important for receptor-binding. Our HC/FA structure also contains a previously unidentified disulphide bond, which we have also observed in one of two crystal forms of HC/A1. This may have implications for receptor-binding and future recombinant toxin production.
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spelling doaj.art-4220cb3abb9f473c8bdcc9788b5693a22023-12-02T23:45:19ZengPeerJ Inc.PeerJ2167-83592018-03-016e455210.7717/peerj.4552High resolution crystal structures of the receptor-binding domain of Clostridium botulinum neurotoxin serotypes A and FAJonathan R. Davies0Gavin S. Hackett1Sai Man Liu2K. Ravi Acharya3Department of Biology and Biochemistry, University of Bath, Bath, United KingdomIpsen Bioinnovation Limited, Abingdon, United KingdomIpsen Bioinnovation Limited, Abingdon, United KingdomDepartment of Biology and Biochemistry, University of Bath, Bath, United KingdomThe 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 (HN) and a receptor-binding domain (HC). Here we report the crystal structure of HC/FA, complementing an existing structure through the modelling of a previously unresolved loop which is important for receptor-binding. Our HC/FA structure also contains a previously unidentified disulphide bond, which we have also observed in one of two crystal forms of HC/A1. This may have implications for receptor-binding and future recombinant toxin production.https://peerj.com/articles/4552.pdfSV2Crystal structureBotulinum neurotoxinTargeted secretion inhibitorFA hybridReceptor binding domain
spellingShingle Jonathan R. Davies
Gavin S. Hackett
Sai Man Liu
K. Ravi Acharya
High resolution crystal structures of the receptor-binding domain of Clostridium botulinum neurotoxin serotypes A and FA
PeerJ
SV2
Crystal structure
Botulinum neurotoxin
Targeted secretion inhibitor
FA hybrid
Receptor binding domain
title High resolution crystal structures of the receptor-binding domain of Clostridium botulinum neurotoxin serotypes A and FA
title_full High resolution crystal structures of the receptor-binding domain of Clostridium botulinum neurotoxin serotypes A and FA
title_fullStr High resolution crystal structures of the receptor-binding domain of Clostridium botulinum neurotoxin serotypes A and FA
title_full_unstemmed High resolution crystal structures of the receptor-binding domain of Clostridium botulinum neurotoxin serotypes A and FA
title_short High resolution crystal structures of the receptor-binding domain of Clostridium botulinum neurotoxin serotypes A and FA
title_sort high resolution crystal structures of the receptor binding domain of clostridium botulinum neurotoxin serotypes a and fa
topic SV2
Crystal structure
Botulinum neurotoxin
Targeted secretion inhibitor
FA hybrid
Receptor binding domain
url https://peerj.com/articles/4552.pdf
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