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6ZVM

Botulinum neurotoxin B2 binding domain in complex with GD1a

This is a non-PDB format compatible entry.
Summary for 6ZVM
Entry DOI10.2210/pdb6zvm/pdb
DescriptorNeurotoxin, N-acetyl-alpha-neuraminic acid-(2-3)-beta-D-galactopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-galactopyranose-(1-4)-[N-acetyl-alpha-neuraminic acid-(2-3)]beta-D-galactopyranose-(1-4)-beta-D-glucopyranose, GLYCEROL, ... (4 entities in total)
Functional Keywordsbotulinum neurotoxin, ganglioside, gd1a, bont, b2, toxin
Biological sourceClostridium botulinum
Total number of polymer chains1
Total formula weight53939.22
Authors
Davies, J.R.,Masuyer, G.,Stenmark, P. (deposition date: 2020-07-25, release date: 2020-10-14, Last modification date: 2024-01-31)
Primary citationDavies, J.R.,Masuyer, G.,Stenmark, P.
Structural and Biochemical Characterization of Botulinum Neurotoxin Subtype B2 Binding to Its Receptors.
Toxins, 12:-, 2020
Cited by
PubMed Abstract: Botulinum neurotoxins (BoNTs) can be used therapeutically to treat a wide range of neuromuscular and neurological conditions. A collection of natural BoNT variants exists which can be classified into serologically distinct serotypes (BoNT/B), and further divided into subtypes (BoNT/B1, B2, …). BoNT subtypes share a high degree of sequence identity within the same serotype yet can display large variation in toxicity. One such example is BoNT/B2, which was isolated from strain 111 in a clinical case of botulism, and presents a 10-fold lower toxicity than BoNT/B1. In an effort to understand the molecular mechanisms behind this difference in potency, we here present the crystal structures of BoNT/B2 in complex with the ganglioside receptor GD1a, and with the human synaptotagmin I protein receptor. We show, using receptor-binding assays, that BoNT/B2 has a slightly higher affinity for GD1a than BoNT/B1, and confirm its considerably weaker affinity for its protein receptors. Although the overall receptor-binding mechanism is conserved for both receptors, structural analysis suggests the lower affinity of BoNT/B2 is the result of key substitutions, where hydrophobic interactions important for synaptotagmin-binding are replaced by polar residues. This study provides a template to drive the development of future BoNT therapeutic molecules centered on assessing the natural subtype variations in receptor-binding that appears to be one of the principal stages driving toxicity.
PubMed: 32957706
DOI: 10.3390/toxins12090603
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.8 Å)
Structure validation

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