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

Kyle S GregorySai Man LiuK Ravi Acharya
Published in: FEBS open bio (2020)
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.
Keyphrases
  • single cell
  • binding protein
  • cell therapy
  • dna binding
  • stem cells
  • small molecule
  • mesenchymal stem cells
  • molecular dynamics
  • amino acid
  • protein protein
  • transcription factor
  • bone marrow
  • brain injury
  • crystal structure