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Open data
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Basic information
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Title | Structure of synaptic vesicle protein 2B with padsevonil | |||||||||
![]() | Main map sharpened | |||||||||
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![]() | Synaptic vesicle / SLC22 / Inhibitor / Antiepileptic / TRANSPORT PROTEIN | |||||||||
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 | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
![]() | Martin MF / Mittal A / Levin E / Adams C / Yang M / Ledecq M / Horanyi PS / Coleman JA | |||||||||
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. | |||||||||
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 136.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 21.2 KB 21.2 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 11.1 KB | Display | ![]() |
Images | ![]() | 36 KB | ||
Masks | ![]() ![]() | 144.7 MB 144.7 MB | ![]() | |
Filedesc metadata | ![]() | 7.1 KB | ||
Others | ![]() ![]() ![]() | 72.2 MB 134.1 MB 134.1 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 1.2 MB | Display | ![]() |
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Full document | ![]() | 1.2 MB | Display | |
Data in XML | ![]() | 19.8 KB | Display | |
Data in CIF | ![]() | 25.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8uo8MC ![]() 8uo9C ![]() 8uoaC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Main map sharpened | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.72 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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-Additional map: Unsharpened map
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-Half map: Half map B
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-Half map: Half map A
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Sample components
-Entire : SV2B complexed with padsevonil
Entire | Name: SV2B complexed with padsevonil |
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Components |
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-Supramolecule #1: SV2B complexed with padsevonil
Supramolecule | Name: SV2B complexed with padsevonil / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 77.4 kDa/nm |
-Macromolecule #1: Synaptic vesicle glycoprotein 2B
Macromolecule | Name: Synaptic vesicle glycoprotein 2B / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 77.515016 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MDDYKYQDNY GGYAPSDGYY RGNESNPEED AQSDVTEGHD EEDEIYEGEY QGIPHPDDVK AKQAKMAPSR MDSLRGQTDL MAERLEDEE QLAHQYETIM DECGHGRFQW ILFFVLGLAL MADGVEVFVV SFALPSAEKD MCLSSSKKGM LGMIVYLGMM A GAFILGGL ...String: MDDYKYQDNY GGYAPSDGYY RGNESNPEED AQSDVTEGHD EEDEIYEGEY QGIPHPDDVK AKQAKMAPSR MDSLRGQTDL MAERLEDEE QLAHQYETIM DECGHGRFQW ILFFVLGLAL MADGVEVFVV SFALPSAEKD MCLSSSKKGM LGMIVYLGMM A GAFILGGL ADKLGRKRVL SMSLAVNASF ASLSSFVQGY GAFLFCRLIS GIGIGGALPI VFAYFSEFLS REKRGEHLSW LG IFWMTGG LYASAMAWSI IPHYGWGFSM GTNYHFHSWR VFVIVCALPC TVSMVALKFM PESPRFLLEM GKHDEAWMIL KQV HDTNMR AKGTPEKVFT VSNIKTPKQM DEFIEIQSST GTWYQRWLVR FKTIFKQVWD NALYCVMGPY RMNTLILAVV WFAM AFSYY GLTVWFPDMI RYFQDEEYKS KMKVFFGEHV YGATINFTME NQIHQHGKLV NDKFTRMYFK HVLFEDTFFD ECYFE DVTS TDTYFKNCTI ESTIFYNTDL YEHKFINCRF INSTFLEQKE GCHMDLEQDN DFLIYLVSFL GSLSVLPGNI ISALLM DRI GRLKMIGGSM LISAVCCFFL FFGNSESAMI GWQCLFCGTS IAAWNALDVI TVELYPTNQR ATAFGILNGL CKFGAIL GN TIFASFVGIT KVVPILLAAA SLVGGGLIAL RLPETREQVL M UniProtKB: Synaptic vesicle glycoprotein 2B |
-Macromolecule #2: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 2 / Number of copies: 3 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Macromolecule #3: (4R)-4-(2-chloro-2,2-difluoroethyl)-1-{[(4R)-2-(methoxymethyl)-6-...
Macromolecule | Name: (4R)-4-(2-chloro-2,2-difluoroethyl)-1-{[(4R)-2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}pyrrolidin-2-one type: ligand / ID: 3 / Number of copies: 1 / Formula: X3U |
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Molecular weight | Theoretical: 432.797 Da |
-Macromolecule #4: 1,2-DIDECANOYL-SN-GLYCERO-3-[PHOSPHO-L-SERINE]
Macromolecule | Name: 1,2-DIDECANOYL-SN-GLYCERO-3-[PHOSPHO-L-SERINE] / type: ligand / ID: 4 / Number of copies: 1 / Formula: PS1 |
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Molecular weight | Theoretical: 566.642 Da |
Chemical component information | ![]() ChemComp-PS1: |
-Macromolecule #5: (3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]sp...
Macromolecule | Name: (3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]spirost-5-en type: ligand / ID: 5 / Number of copies: 2 / Formula: 9Z9 |
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Molecular weight | Theoretical: 544.805 Da |
Chemical component information | ![]() ChemComp-9Z9: |
-Macromolecule #6: [(2R)-3-[oxidanyl-[2-(trimethyl-$l^{4}-azanyl)ethoxy]phosphoryl]o...
Macromolecule | Name: [(2R)-3-[oxidanyl-[2-(trimethyl-$l^{4}-azanyl)ethoxy]phosphoryl]oxy-2-propanoyloxy-propyl] propanoate type: ligand / ID: 6 / Number of copies: 1 / Formula: 43Y |
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Molecular weight | Theoretical: 370.356 Da |
Chemical component information | ![]() ChemComp-43Y: |
-Macromolecule #7: CHOLESTEROL HEMISUCCINATE
Macromolecule | Name: CHOLESTEROL HEMISUCCINATE / type: ligand / ID: 7 / Number of copies: 1 / Formula: Y01 |
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Molecular weight | Theoretical: 486.726 Da |
Chemical component information | ![]() ChemComp-Y01: |
-Macromolecule #8: water
Macromolecule | Name: water / type: ligand / ID: 8 / Number of copies: 5 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ![]() ChemComp-HOH: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 4 mg/mL |
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Buffer | pH: 8 Details: 150 mM NaCl, 20 mM Tris pH 8.0, .4 mM glyco-diosgenin, 1 uM padsevonil |
Grid | Model: Quantifoil R2/1 / Material: GOLD / Mesh: 200 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 30 sec. / Pretreatment - Atmosphere: AIR |
Vitrification | Cryogen name: ETHANE-PROPANE / Chamber humidity: 100 % / Chamber temperature: 298 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | TFS KRIOS |
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Specialist optics | Energy filter - Name: TFS Selectris / Energy filter - Slit width: 10 eV |
Image recording | Film or detector model: TFS FALCON 4i (4k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.5 µm / Nominal magnification: 194000 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |