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Crystal structure of botulinum neurotoxin subtype A3 cell binding domain in complex with GD1a co‐receptor ganglioside

DOI: 10.1002/2211-5463.12790 DOI Help

Authors: Kyle S. Gregory (University of Bath) , Sai Man Liu (Ipsen Bioinnovation Limited) , K. Ravi Acharya (University of Bath)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Febs Open Bio

State: Published (Approved)
Published: January 2020
Diamond Proposal Number(s): 17212

Open Access Open Access

Abstract: Botulinum neurotoxins (BoNTs) are one of the most toxic proteins known to humans. Their molecular structure is comprised of three essential domains – a cell binding domain (HC), translocation domain (HN), and catalytic domain (LC). The HC domain facilitates the highly specific binding of BoNTs to the neuronal membrane via a dual‐receptor complex involving a protein receptor and a ganglioside. Variation in activity/toxicity across subtypes of serotype A has been attributed to changes in protein and ganglioside interactions and their implications are important in the design of novel BoNT‐based therapeutics. Here, we present the structure of BoNT/A3 cell binding domain (HC/A3) in complex with the ganglioside GD1a at 1.75 Å resolution. The structure revealed that six residues interact with the three outermost monosaccharides of GD1a through several key hydrogen bonding interactions. A detailed comparison of structures of HC/A3 with HC/A1 revealed subtle conformational differences at the ganglioside binding site (GBS) upon carbohydrate binding.

Journal Keywords: Botulinum neurotoxin; ganglioside binding; cell binding domain; protein structure; crystallography

Subject Areas: Biology and Bio-materials


Instruments: I04-Macromolecular Crystallography

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