| Structural highlights
8uo8 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | Electron Microscopy, Resolution 3.2Å |
| Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
SV2B_HUMAN Probably plays a role in the control of regulated secretion in neural and endocrine cells. (Microbial infection) Receptor for the C.botulinum neurotoxin type A2 (BoNT/A, botA); glycosylation is not essential but enhances the interaction (PubMed:29649119). Probably also serves as a receptor for the closely related C.botulinum neurotoxin type A1.[1] [2]
Publication Abstract from PubMed
Epilepsy is a common neurological disorder characterized by abnormal activity of neuronal networks, leading to seizures. The racetam class of anti-seizure medications bind specifically to a membrane protein found in the synaptic vesicles of neurons called synaptic vesicle protein 2 (SV2) A (SV2A). SV2A belongs to an orphan subfamily of the solute carrier 22 organic ion transporter family that also includes SV2B and SV2C. The molecular basis for how anti-seizure medications act on SV2s remains unknown. Here we report cryo-electron microscopy structures of SV2A and SV2B captured in a luminal-occluded conformation complexed with anticonvulsant ligands. The conformation bound by anticonvulsants resembles an inhibited transporter with closed luminal and intracellular gates. Anticonvulsants bind to a highly conserved central site in SV2s. These structures provide blueprints for future drug design and will facilitate future investigations into the biological function of SV2s.
Structures of synaptic vesicle protein 2A and 2B bound to anticonvulsants.,Mittal A, Martin MF, Levin EJ, Adams C, Yang M, Provins L, Hall A, Procter M, Ledecq M, Hillisch A, Wolff C, Gillard M, Horanyi PS, Coleman JA Nat Struct Mol Biol. 2024 Jun 19. doi: 10.1038/s41594-024-01335-1. PMID:38898101[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gustafsson R, Zhang S, Masuyer G, Dong M, Stenmark P. Crystal Structure of Botulinum Neurotoxin A2 in Complex with the Human Protein Receptor SV2C Reveals Plasticity in Receptor Binding. Toxins (Basel). 2018 Apr 12;10(4). pii: toxins10040153. doi:, 10.3390/toxins10040153. PMID:29649119 doi:http://dx.doi.org/10.3390/toxins10040153
- ↑ Gustafsson R, Zhang S, Masuyer G, Dong M, Stenmark P. Crystal Structure of Botulinum Neurotoxin A2 in Complex with the Human Protein Receptor SV2C Reveals Plasticity in Receptor Binding. Toxins (Basel). 2018 Apr 12;10(4). pii: toxins10040153. doi:, 10.3390/toxins10040153. PMID:29649119 doi:http://dx.doi.org/10.3390/toxins10040153
- ↑ Mittal A, Martin MF, Levin EJ, Adams C, Yang M, Provins L, Hall A, Procter M, Ledecq M, Hillisch A, Wolff C, Gillard M, Horanyi PS, Coleman JA. Structures of synaptic vesicle protein 2A and 2B bound to anticonvulsants. Nat Struct Mol Biol. 2024 Jun 19. PMID:38898101 doi:10.1038/s41594-024-01335-1
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