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Yorodumi- PDB-8uo9: Structure of synaptic vesicle protein 2A in complex with a nanobody -
+Open data
-Basic information
Entry | Database: PDB / ID: 8uo9 | |||||||||
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Title | Structure of synaptic vesicle protein 2A in complex with a nanobody | |||||||||
Components |
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Keywords | TRANSPORT PROTEIN / Synaptic vesicle / SLC22 / Inhibitor / Nanobody / AEDs | |||||||||
Function / homology | Function and homology information regulation of gamma-aminobutyric acid secretion / 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) / synaptic vesicle priming / presynaptic active zone / transmembrane transporter activity / GABA-ergic synapse / neuromuscular junction ...regulation of gamma-aminobutyric acid secretion / 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) / synaptic vesicle priming / presynaptic active zone / transmembrane transporter activity / GABA-ergic synapse / neuromuscular junction / intracellular calcium ion homeostasis / synaptic vesicle membrane / cell-cell junction / synaptic vesicle / neuron projection / neuronal cell body / glutamatergic synapse / dendrite / protein kinase binding / endoplasmic reticulum / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) Lama glama (llama) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
Authors | Mittal, A. / Martin, M.F. / Levin, E. / Adams, C. / Yang, M. / Ledecq, M. / Horanyi, P.S. / Coleman, J.A. | |||||||||
Funding support | United States, 1items
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Citation | Journal: Nat Struct Mol Biol / Year: 2024 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: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8uo9.cif.gz | 149.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8uo9.ent.gz | 106.9 KB | Display | PDB format |
PDBx/mmJSON format | 8uo9.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8uo9_validation.pdf.gz | 1.7 MB | Display | wwPDB validaton report |
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Full document | 8uo9_full_validation.pdf.gz | 1.7 MB | Display | |
Data in XML | 8uo9_validation.xml.gz | 40.4 KB | Display | |
Data in CIF | 8uo9_validation.cif.gz | 57.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/uo/8uo9 ftp://data.pdbj.org/pub/pdb/validation_reports/uo/8uo9 | HTTPS FTP |
-Related structure data
Related structure data | 42431MC 8uo8C 8uoaC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein / Antibody , 2 types, 2 molecules AB
#1: Protein | Mass: 75589.188 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SV2A / Cell line (production host): tsA201 / Production host: Homo sapiens (human) / References: UniProt: Q7L0J3 |
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#2: Antibody | Mass: 15469.103 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Lama glama (llama) / Production host: Escherichia coli (E. coli) |
-Sugars , 2 types, 3 molecules
#3: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
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#4: Polysaccharide | Source method: isolated from a genetically manipulated source |
-Non-polymers , 3 types, 3 molecules
#5: Chemical | ChemComp-X49 / ( Mass: 444.395 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C16H18F6N4O2S / Feature type: SUBJECT OF INVESTIGATION |
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#6: Chemical | ChemComp-Y01 / |
#7: Chemical | ChemComp-PS1 / |
-Details
Has ligand of interest | Y |
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Has protein modification | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Protein with a nanobody / Type: COMPLEX / Entity ID: #2 / Source: MULTIPLE SOURCES |
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Molecular weight | Value: 98.1 kDa/nm / Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 8 |
Specimen | Conc.: 4.38 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 |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 77160 X / Nominal defocus max: 2800 nm / Nominal defocus min: 750 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
EM imaging optics | Energyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV |
-Processing
Image processing |
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CTF correction |
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3D reconstruction |
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Atomic model building | Accession code: AF-Q7L0J3-F1 / Source name: AlphaFold / Type: in silico model | |||||||||||||||||||||||||||||||||||
Refinement | Highest resolution: 3.3 Å |