7uia

Crystal structure of BoNT/E receptor binding domain in complex with SV2 and VHH

spinqualitylabelsall models 7uia, resolution 2.59Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7uia is a 6 chain structure with sequence from Clostridium botulinum, Homo sapiens and Vicugna pacos. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.59Å Ligands: NAG, PEG, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Botulinum neurotoxin E (BoNT/E) is one of the major causes of human botulism and paradoxically also a promising therapeutic agent. Here we determined the co-crystal structures of the receptor-binding domain of BoNT/E (H(C)E) in complex with its neuronal receptor synaptic vesicle glycoprotein 2A (SV2A) and a nanobody that serves as a ganglioside surrogate. These structures reveal that the protein-protein interactions between H(C)E and SV2 provide the crucial location and specificity information for H(C)E to recognize SV2A and SV2B, but not the closely related SV2C. At the same time, H(C)E exploits a separated sialic acid-binding pocket to mediate recognition of an N-glycan of SV2. Structure-based mutagenesis and functional studies demonstrate that both the protein-protein and protein-glycan associations are essential for SV2A-mediated cell entry of BoNT/E and for its potent neurotoxicity. Our studies establish the structural basis to understand the receptor-specificity of BoNT/E and to engineer BoNT/E variants for new clinical applications. Structural basis for botulinum neurotoxin E recognition of synaptic vesicle protein 2.,Liu Z, Lee PG, Krez N, Lam KH, Liu H, Przykopanski A, Chen P, Yao G, Zhang S, Tremblay JM, Perry K, Shoemaker CB, Rummel A, Dong M, Jin R Nat Commun. 2023 Apr 24;14(1):2338. doi: 10.1038/s41467-023-37860-8. PMID:37095076 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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