8RVH

Structure of the binding domain of BoNT/A mutant Y1117V/H1253K in complex with the GD1a ganglioside receptor

Summary for 8RVH

• Entry DOI: 10.2210/pdb8rvh/pdb
• Descriptor: Botulinum neurotoxin A heavy chain, beta-D-galactopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-galactopyranose-(1-4)-beta-D-galactopyranose-(1-4)-beta-D-glucopyranose, N-acetyl-alpha-neuraminic acid, ... (4 entities in total)
• Functional Keywords: botulinum neurotoxin, receptor binding, ganglioside, toxin
• Biological source: Clostridium botulinum
• Total number of polymer chains: 1
• Total formula weight: 52966.56

Authors

Masuyer, G.,Stenmark, P. (deposition date: 2024-02-01, release date: 2025-02-12, Last modification date: 2025-08-27)

Primary citation

Masuyer, G.,Rummel, A.,Stenmark, P.
Botulinum neurotoxin A mutants with enhanced ganglioside binding show improved potency and altered ganglioside selectivity.
Commun Chem, 8:171-171, 2025

PubMed Abstract: Botulinum neurotoxins are the causative agents of botulism, a lethal paralytic disease, but are also one of the most commonly used therapeutics for the treatment of numerous neuromuscular conditions. These toxins recognise motor nerve terminals with high specificity and affinity by using a dual binding mechanism involving gangliosides and protein receptors. The initial recognition of gangliosides is crucial for the toxins' potency. In this study, we employed a synaptosome-binding screening strategy to identify BoNT/A mutants with enhanced ganglioside-binding which translated into improved potency. X-ray crystallography and receptor-binding assays were used to elucidate the molecular mechanisms underlying the increased affinity or altered ganglioside selectivity of these mutants. Our findings provide a basis for the development of BoNT/A variants with enhanced therapeutic potential.

PubMed: 40467754
DOI: 10.1038/s42004-025-01569-0

Experimental method

X-RAY DIFFRACTION (1.8 Å)