ArticleNature structural & molecular biology2024
Structures of synaptic vesicle protein 2A and 2B bound to anticonvulsants.
Article in Nature structural & molecular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.
What it found
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The trial behind it
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Who cites it
11 citing papers in PubMed.
- Discovery of Selective Small-Molecule Ligands of SV2C by AI-Enhanced Virtual Screening and Experimental Validation.bioRxiv : the preprint server for biology · 2026Article
- Structural Determinants of Synaptic Vesicle Protein 2C Ligand Selectivity and Their Impact on Dopamine Release.bioRxiv : the preprint server for biology · 2026Article
- Imaging Synaptic Vesicle Protein SV2C withACS chemical neuroscience · 2026Article
- Integrative Structural Bioinformatics and Molecular Dynamics Analyses of Synaptic Vesicle Proteins and Their Water-Soluble QTY-Variants Reveal Membrane Constraints and Evolutionary Coupling of T ⇔ V.Journal of molecular evolution · 2026Article
- SV2B Promotes the Progression of TFE3-Rearranged Renal Cell Carcinoma by Interacting with HERC2 to Impede the Degradation of NF-κB Subunits.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Structural pharmacology of SV2A reveals an allosteric modulation mechanism in the major facilitator superfamily.Nature communications · 2025Article
- Mechanisms underlying allosteric modulation of antiseizure medication binding to synaptic vesicle protein 2A (SV2A).Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Structures of native SV2A reveal the binding mode for tetanus neurotoxin and anti-epileptic racetams.Nature communications · 2025Article
- Evaluation of Small-Molecule Candidates as Modulators of M-Type KInternational journal of molecular sciences · 2025Review
- Cryo-EM structure of the botulinum neurotoxin A/SV2B complex and its implications for translocation.Nature communications · 2025Article
- Control of Synaptotagmin-1 Trafficking by SV2A-Mechanism and Consequences for Presynaptic Function and Dysfunction.Journal of neurochemistry · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.