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

Autor: Kyle S. Gregory, Sai Man Liu, K. Ravi Acharya
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: FEBS Open Bio, Vol 10, Iss 3, Pp 298-305 (2020)
Druh dokumentu: article
ISSN: 2211-5463
31786405
DOI: 10.1002/2211-5463.12790
Popis: 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 and catalytic domain (light chain) . 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 upon carbohydrate binding.
Databáze: Directory of Open Access Journals
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