6zvm

Botulinum neurotoxin B2 binding domain in complex with GD1aBotulinum neurotoxin B2 binding domain in complex with GD1a

Structural highlights 6zvm is a 1 chain structure with sequence from Clostridium botulinum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.8Å Ligands: , , , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q8GR96_CLOBO Publication Abstract from PubMed 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 Clostridium botulinum 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. Structural and Biochemical Characterization of Botulinum Neurotoxin Subtype B2 Binding to Its Receptors.,Davies JR, Masuyer G, Stenmark P Toxins (Basel). 2020 Sep 17;12(9). pii: toxins12090603. doi:, 10.3390/toxins12090603. PMID:32957706 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Botulinum neurotoxin 3D structures

spinqualitylabelsall models 6zvm, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image