High-resolution crystal structures of the botulinum neurotoxin binding domains from subtypes A5 and A6

Jonathan R. Davies; Amy Britton; Sai Man Liu; K. Ravi Acharya

doi:10.1002/2211-5463.12931

High-resolution crystal structures of the botulinum neurotoxin binding domains from subtypes A5 and A6

Jonathan R. Davies, Amy Britton, Sai Man Liu, K. Ravi Acharya

Department of Life Sciences

Research output: Contribution to journal › Article › peer-review

7 Citations (SciVal)

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 (H_C), a translocation domain (H_N) and a catalytic domain (LC). Here, we present high-resolution crystal structures of the binding domains of BoNT subtypes/A5 (H_C/A5) and/A6 (H_C/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
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	https://doi.org/10.1002/2211-5463.12931
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

Access to Document

10.1002/2211-5463.12931Licence: CC BY

https://febs.onlinelibrary.wiley.com/doi/full/10.1002/2211-5463.12931

Cite this

@article{6353cce678ff4171aefa2640d3847384,

title = "High-resolution crystal structures of the botulinum neurotoxin binding domains from subtypes A5 and A6",

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.",

keywords = "binding domain structure, botulinum neurotoxin, Clostridium botulinum, subtypes, X-ray crystallography",

author = "Davies, \{Jonathan R.\} and Amy Britton and Liu, \{Sai Man\} and Acharya, \{K. Ravi\}",

year = "2020",

month = aug,

day = "1",

doi = "10.1002/2211-5463.12931",

language = "English",

volume = "10",

pages = "1474--1481",

journal = "FEBS Open Bio",

issn = "2211-5463",

publisher = "John Wiley and Sons Inc.",

number = "8",

}

TY - JOUR

T1 - High-resolution crystal structures of the botulinum neurotoxin binding domains from subtypes A5 and A6

AU - Davies, Jonathan R.

AU - Britton, Amy

AU - Liu, Sai Man

AU - Acharya, K. Ravi

PY - 2020/8/1

Y1 - 2020/8/1

N2 - 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.

AB - 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.

KW - binding domain structure

KW - botulinum neurotoxin

KW - Clostridium botulinum

KW - subtypes

KW - X-ray crystallography

UR - https://www.scopus.com/pages/publications/85088311886

U2 - 10.1002/2211-5463.12931

DO - 10.1002/2211-5463.12931

M3 - Article

C2 - 32654405

AN - SCOPUS:85088311886

SN - 2211-5463

VL - 10

SP - 1474

EP - 1481

JO - FEBS Open Bio

JF - FEBS Open Bio

IS - 8

ER -

High-resolution crystal structures of the botulinum neurotoxin binding domains from subtypes A5 and A6

Abstract

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this