6THY

Botulinum neurotoxin A3 Hc domain in complex with GD1a

This is a non-PDB format compatible entry.

Summary for 6THY

• Entry DOI: 10.2210/pdb6thy/pdb
• Related: 2vu9 5tpc 6f0o
• Descriptor: BoNT/A3, N-acetyl-alpha-neuraminic acid-(2-3)-beta-D-galactopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-galactopyranose-(1-4)-beta-D-galactopyranose-(1-4)-beta-D-glucopyranose, HEXAETHYLENE GLYCOL, ... (7 entities in total)
• Functional Keywords: botulinum, neurotoxin, ganglioside, gd1a, toxin
• Biological source: Clostridium botulinum
• Total number of polymer chains: 1
• Total formula weight: 52141.10

Authors

Gregory, K.S.,Acharya, K.R.,Liu, S.M. (deposition date: 2019-11-21, release date: 2020-01-29, Last modification date: 2024-01-24)

Primary citation

Gregory, K.S.,Liu, S.M.,Acharya, K.R.
Crystal structure of botulinum neurotoxin subtype A3 cell binding domain in complex with GD1a co-receptor ganglioside.
Febs Open Bio, 10:298-305, 2020

PubMed 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 (H ), translocation domain and catalytic domain (light chain) . The H 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 /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 /A3 with H /A1 revealed subtle conformational differences at the ganglioside binding site upon carbohydrate binding.

PubMed: 31945264
DOI: 10.1002/2211-5463.12790

Experimental method

X-RAY DIFFRACTION (1.75 Å)