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Open data
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Basic information
Entry | Database: PDB / ID: 8uo8 | ||||||
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Title | Structure of synaptic vesicle protein 2B with padsevonil | ||||||
![]() | Synaptic vesicle glycoprotein 2B | ||||||
![]() | TRANSPORT PROTEIN / Synaptic vesicle / SLC22 / Inhibitor / Antiepileptic | ||||||
Function / homology | ![]() Toxicity of botulinum toxin type F (botF) / Toxicity of botulinum toxin type D (botD) / Toxicity of botulinum toxin type E (botE) / Toxicity of botulinum toxin type A (botA) / regulation of presynaptic cytosolic calcium ion concentration / neurotransmitter transport / regulation of synaptic vesicle exocytosis / transmembrane transporter activity / acrosomal vesicle / synaptic vesicle membrane ...Toxicity of botulinum toxin type F (botF) / Toxicity of botulinum toxin type D (botD) / Toxicity of botulinum toxin type E (botE) / Toxicity of botulinum toxin type A (botA) / regulation of presynaptic cytosolic calcium ion concentration / neurotransmitter transport / regulation of synaptic vesicle exocytosis / transmembrane transporter activity / acrosomal vesicle / synaptic vesicle membrane / synaptic vesicle / chemical synaptic transmission / membrane / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | ||||||
![]() | Martin, M.F. / Mittal, A. / Levin, E. / Adams, C. / Yang, M. / Ledecq, M. / Horanyi, P.S. / Coleman, J.A. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Structures of synaptic vesicle protein 2A and 2B bound to anticonvulsants. Authors: Anshumali Mittal / Matthew F Martin / Elena J Levin / Christopher Adams / Meng Yang / Laurent Provins / Adrian Hall / Martin Procter / Marie Ledecq / Alexander Hillisch / Christian Wolff / ...Authors: Anshumali Mittal / Matthew F Martin / Elena J Levin / Christopher Adams / Meng Yang / Laurent Provins / Adrian Hall / Martin Procter / Marie Ledecq / Alexander Hillisch / Christian Wolff / Michel Gillard / Peter S Horanyi / Jonathan A Coleman / ![]() ![]() ![]() ![]() 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 ...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. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 123.8 KB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.9 MB | Display | ![]() |
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Full document | ![]() | 1.9 MB | Display | |
Data in XML | ![]() | 38 KB | Display | |
Data in CIF | ![]() | 53.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 42430MC ![]() 8uo9C ![]() 8uoaC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
-Protein / Sugars , 2 types, 4 molecules A![](data/chem/img/NAG.gif)
![](data/chem/img/NAG.gif)
#1: Protein | Mass: 77515.016 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#2: Sugar |
-Non-polymers , 6 types, 11 molecules ![](data/chem/img/PS1.gif)
![](data/chem/img/9Z9.gif)
![](data/chem/img/43Y.gif)
![](data/chem/img/Y01.gif)
![](data/chem/img/HOH.gif)
![](data/chem/img/9Z9.gif)
![](data/chem/img/43Y.gif)
![](data/chem/img/Y01.gif)
![](data/chem/img/HOH.gif)
#3: Chemical | ChemComp-X3U / ( Mass: 432.797 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C14H14ClF5N4O2S / Feature type: SUBJECT OF INVESTIGATION | ||||||
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#4: Chemical | ChemComp-PS1 / | ||||||
#5: Chemical | #6: Chemical | ChemComp-43Y / [( | #7: Chemical | ChemComp-Y01 / | #8: Water | ChemComp-HOH / | |
-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: SV2B complexed with padsevonil / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Molecular weight | Value: 77.4 kDa/nm / Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 8 Details: 150 mM NaCl, 20 mM Tris pH 8.0, .4 mM glyco-diosgenin, 1 uM padsevonil |
Specimen | Conc.: 4 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: GOLD / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R2/1 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE-PROPANE / Humidity: 100 % / Chamber temperature: 298 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 194000 X / Nominal defocus max: 1500 nm / Nominal defocus min: 500 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: TFS FALCON 4i (4k x 4k) |
EM imaging optics | Energyfilter name: TFS Selectris / Energyfilter slit width: 10 eV |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 62528 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Accession code: AF-Q7L1I2-F1 / Source name: AlphaFold / Type: in silico model | ||||||||||||||||||||||||
Refine LS restraints |
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