9fyq

Cryo-EM structure of native SV2A in complex with TeNT-Hc, gangliosides and Pro-Macrobody 5

spinqualitylabelsall models 9fyq, resolution 3.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9fyq is a 3 chain structure with sequence from Clostridium tetani E88, Escherichia coli K-12, Lama glama and Ovis aries. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.25Å Ligands: 6UZ, A1IHM, A1IHN, FUC, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A836APF1_SHEEP Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily releasable pool of secretory vesicles.[ARBA:ARBA00037074] Publication Abstract from PubMed The synaptic vesicle glycoprotein 2A (SV2A) is a synaptic vesicle (SV) resident with homology to the major facilitator superfamily (MFS) and essential in vertebrate neurotransmission. Despite its unclear physiological role, SV2A is of high medical relevance as it is the target of the anti-epileptic drug Levetiracetam (LEV) and a receptor for clostridial neurotoxins (CNTs), among them presumably tetanus neurotoxin (TeNT). To obtain detailed insights about these molecular interactions we subjected native SV2A, purified from brain tissue, to cryo-EM. We discover that TeNT binds SV2A strikingly different from botulinum neurotoxin A and unveil the precise geometry of TeNT binding to dipartite SV2-ganglioside receptors. The structures deliver compelling support for SV2A as the protein receptor for TeNT in central neurons and reinforce the concepts of the dual receptor hypothesis for CNT entry into neurons. Further, our LEV-bound structure of SV2A reveals the drug-interacting residues, delineates a putative substrate pocket in SV2A and provides insights into the SV2-isoform-specificity of LEV. Our work has implications for CNT engineering from a hitherto unrecognized SV2 binding interface and for improved designs of anti-convulsant drugs in epilepsy treatment. Structures of native SV2A reveal the binding mode for tetanus neurotoxin and anti-epileptic racetams.,Schenck S, Laeremans T, Steyaert J, Brunner JD Nat Commun. 2025 May 5;16(1):4172. doi: 10.1038/s41467-025-59545-0. PMID:40325068 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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