Open AccessCrystal structure of botulinum neurotoxin subtype A3 cell binding domain in complex with GD1a co‐receptor ganglioside
Author(s) -
Gregory Kyle S.,
Liu Sai Man,
Acharya K. Ravi
Publication year - 2020
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12790
Subject(s) - ganglioside , chemistry , receptor , protein structure , binding site , biochemistry , biophysics , biology , microbiology and biotechnology
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 (H C ), translocation domain and catalytic domain (light chain) . The H C 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 (H C /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 H C /A3 with H C /A1 revealed subtle conformational differences at the ganglioside binding site upon carbohydrate binding.