6thy

Publication Abstract from PubMed

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 A 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.

Crystal structure of botulinum neurotoxin subtype A3 cell binding domain in complex with GD1a co-receptor ganglioside.,Gregory KS, Liu SM, Acharya KR FEBS Open Bio. 2020 Jan 16. doi: 10.1002/2211-5463.12790. PMID:31945264^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.