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Yorodumi- EMDB-9151: Diheteromeric NMDA receptor GluN1/GluN2A in the 'Extended-2' conf... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-9151 | |||||||||
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Title | Diheteromeric NMDA receptor GluN1/GluN2A in the 'Extended-2' conformation, in complex with glycine and glutamate, in the presence of 1 millimolar zinc chloride, and at pH 7.4 | |||||||||
Map data | Diheteromeric NMDA receptor GluN1/GluN2A in the 'Extended-2' conformation, in complex with glycine and glutamate, in the presence of 1 millimolar zinc chloride, and at pH 7.4 | |||||||||
Sample |
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Function / homology | Function and homology information neurotransmitter receptor transport, plasma membrane to endosome / regulation of response to alcohol / response to ammonium ion / receptor recycling / directional locomotion / conditioned place preference / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / response to environmental enrichment ...neurotransmitter receptor transport, plasma membrane to endosome / regulation of response to alcohol / response to ammonium ion / receptor recycling / directional locomotion / conditioned place preference / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / response to environmental enrichment / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / response to hydrogen sulfide / olfactory learning / serotonin metabolic process / conditioned taste aversion / dendritic branch / regulation of respiratory gaseous exchange / protein localization to postsynaptic membrane / response to other organism / positive regulation of inhibitory postsynaptic potential / propylene metabolic process / response to glycine / regulation of ARF protein signal transduction / cellular response to magnesium ion / response to methylmercury / sleep / voltage-gated monoatomic cation channel activity / cellular response to dsRNA / dendritic spine organization / response to carbohydrate / locomotion / regulation of monoatomic cation transmembrane transport / response to morphine / cellular response to lipid / NMDA glutamate receptor activity / Synaptic adhesion-like molecules / RAF/MAP kinase cascade / NMDA selective glutamate receptor complex / glutamate-gated calcium ion channel activity / parallel fiber to Purkinje cell synapse / response to manganese ion / calcium ion transmembrane import into cytosol / regulation of NMDA receptor activity / protein heterotetramerization / glutamate binding / cellular response to zinc ion / positive regulation of reactive oxygen species biosynthetic process / neuromuscular process / regulation of synapse assembly / action potential / glycine binding / positive regulation of calcium ion transport into cytosol / regulation of dendrite morphogenesis / male mating behavior / regulation of axonogenesis / spinal cord development / dopamine metabolic process / suckling behavior / startle response / monoatomic cation transmembrane transport / regulation of neuronal synaptic plasticity / response to amine / modulation of excitatory postsynaptic potential / response to lithium ion / social behavior / associative learning / positive regulation of excitatory postsynaptic potential / monoatomic cation transport / ligand-gated monoatomic ion channel activity / excitatory synapse / cellular response to glycine / positive regulation of dendritic spine maintenance / response to light stimulus / Unblocking of NMDA receptors, glutamate binding and activation / neuron development / positive regulation of protein targeting to membrane / regulation of postsynaptic membrane potential / phosphatase binding / glutamate receptor binding / postsynaptic density, intracellular component / calcium ion homeostasis / cellular response to manganese ion / prepulse inhibition / multicellular organismal response to stress / long-term memory / monoatomic cation channel activity / regulation of neuron apoptotic process / presynaptic active zone membrane / synaptic cleft / glutamate-gated receptor activity / response to fungicide / sensory perception of pain / cell adhesion molecule binding / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / response to amphetamine / ionotropic glutamate receptor signaling pathway / excitatory postsynaptic potential / hippocampal mossy fiber to CA3 synapse Similarity search - Function | |||||||||
Biological species | Rattus norvegicus (Norway rat) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 8.21 Å | |||||||||
Authors | Jalali-Yazdi F / Chowdhury S / Yoshioka C / Gouaux E | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Cell / Year: 2018 Title: Mechanisms for Zinc and Proton Inhibition of the GluN1/GluN2A NMDA Receptor. Authors: Farzad Jalali-Yazdi / Sandipan Chowdhury / Craig Yoshioka / Eric Gouaux / Abstract: N-methyl-D-aspartate receptors (NMDARs) play essential roles in memory formation, neuronal plasticity, and brain development, with their dysfunction linked to a range of disorders from ischemia to ...N-methyl-D-aspartate receptors (NMDARs) play essential roles in memory formation, neuronal plasticity, and brain development, with their dysfunction linked to a range of disorders from ischemia to schizophrenia. Zinc and pH are physiological allosteric modulators of NMDARs, with GluN2A-containing receptors inhibited by nanomolar concentrations of divalent zinc and by excursions to low pH. Despite the widespread importance of zinc and proton modulation of NMDARs, the molecular mechanism by which these ions modulate receptor activity has proven elusive. Here, we use cryoelectron microscopy to elucidate the structure of the GluN1/GluN2A NMDAR in a large ensemble of conformations under a range of physiologically relevant zinc and proton concentrations. We show how zinc binding to the amino terminal domain elicits structural changes that are transduced though the ligand-binding domain and result in constriction of the ion channel gate. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_9151.map.gz | 25.1 MB | EMDB map data format | |
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Header (meta data) | emd-9151-v30.xml emd-9151.xml | 26 KB 26 KB | Display Display | EMDB header |
Images | emd_9151.png | 147 KB | ||
Masks | emd_9151_msk_1.map | 27 MB | Mask map | |
Others | emd_9151_half_map_1.map.gz emd_9151_half_map_2.map.gz | 11 MB 11 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-9151 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9151 | HTTPS FTP |
-Related structure data
Related structure data | 6mmhMC 9147C 9148C 9149C 9150C 9152C 9153C 9154C 9155C 9156C 9157C 9158C 9159C 9160C 9161C 9162C 9163C 9164C 9165C 6mm9C 6mmaC 6mmbC 6mmgC 6mmiC 6mmjC 6mmkC 6mmlC 6mmmC 6mmnC 6mmpC 6mmrC 6mmsC 6mmtC 6mmuC 6mmvC 6mmwC 6mmxC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_9151.map.gz / Format: CCP4 / Size: 27 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Diheteromeric NMDA receptor GluN1/GluN2A in the 'Extended-2' conformation, in complex with glycine and glutamate, in the presence of 1 millimolar zinc chloride, and at pH 7.4 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.71 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_9151_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: Half-maps used for FSC calculations
File | emd_9151_half_map_1.map | ||||||||||||
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Annotation | Half-maps used for FSC calculations | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half-maps used for FSC calculations
File | emd_9151_half_map_2.map | ||||||||||||
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Annotation | Half-maps used for FSC calculations | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Diheteromeric NMDA receptor GluN1/GluN2A in the 'Extended-2' conf...
Entire | Name: Diheteromeric NMDA receptor GluN1/GluN2A in the 'Extended-2' conformation, in complex with glycine and glutamate, in the presence of 1 milliomolar zinc chloride, and at pH 7.4 |
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Components |
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-Supramolecule #1: Diheteromeric NMDA receptor GluN1/GluN2A in the 'Extended-2' conf...
Supramolecule | Name: Diheteromeric NMDA receptor GluN1/GluN2A in the 'Extended-2' conformation, in complex with glycine and glutamate, in the presence of 1 milliomolar zinc chloride, and at pH 7.4 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 Details: Sample was heterologously expressed in TSA-201 cells, detergent solubilized, and affinity purified |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Recombinant expression | Organism: Homo sapiens (human) / Recombinant cell: TSA-201 |
Molecular weight | Theoretical: 500 KDa |
-Macromolecule #1: Glutamate receptor ionotropic, NMDA 1
Macromolecule | Name: Glutamate receptor ionotropic, NMDA 1 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Molecular weight | Theoretical: 94.189781 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MSTMHLLTFA LLFSCSFARA ACDPKIVNIG AVLSTRKHEQ MFREAVNQAN KRHGSWKIQL NATSVTHKPN AIQMALSVCE DLISSQVYA ILVSHPPTPN DHFTPTPVSY TAGFYRIPVL GLTTRMSIYS DKSIHLSFLR TVPPYSHQSS VWFEMMRVYN W NHIILLVS ...String: MSTMHLLTFA LLFSCSFARA ACDPKIVNIG AVLSTRKHEQ MFREAVNQAN KRHGSWKIQL NATSVTHKPN AIQMALSVCE DLISSQVYA ILVSHPPTPN DHFTPTPVSY TAGFYRIPVL GLTTRMSIYS DKSIHLSFLR TVPPYSHQSS VWFEMMRVYN W NHIILLVS DDHEGRAAQK RLETLLEERE SKAEKVLQFD PGTKNVTALL MEARELEARV IILSASEDDA ATVYRAAAML NM TGSGYVW LVGEREISGN ALRYAPDGII GLQLINGKNE SAHISDAVGV VAQAVHELLE KENITDPPRG CVGNTNIWKT GPL FKRVLM SSKYADGVTG RVEFNEDGDR KFANYSIMNL QNRKLVQVGI YNGTHVIPND RKIIWPGGET EKPRGYQMST RLKI VTIHQ EPFVYVKPTM SDGTCKEEFT VNGDPVKKVI CTGPNDTSPG SPRHTVPQCC YGFCIDLLIK LARTMNFTYE VHLVA DGKF GTQERVNNSN KKEWNGMMGE LLSGQADMIV APLTINNERA QYIEFSKPFK YQGLTILVKK EIPRSTLDSF MQPFQS TLW LLVGLSVHVV AVMLYLLDRF SPFGRFKVNS EEEEEDALTL SSAMWFSWGV LLNSGIGEGA PRSFSARILG MVWAGFA MI IVASYTANLA AFLVLDRPEE RITGINDPRL RNPSDKFIYA TVKQSSVDIY FRRQVELSTM YRHMEKHNYE SAAEAIQA V RDNKLHAFIW DSAVLEFEAS QKCDLVTTGE LFFRSGFGIG MRKDSPWKQN VSLSILKSHE NGFMEDLDKT WVRYQECDS RSNAPATLTF ENMAGVFMLV AGGIVAGIFL IFIEIAYK |
-Macromolecule #2: Glutamate receptor ionotropic, NMDA 2A
Macromolecule | Name: Glutamate receptor ionotropic, NMDA 2A / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Molecular weight | Theoretical: 93.740352 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MGRLGYWTLL VLPALLVWRD PAQNAAAEKG PPALNIAVLL GHSHDVTERE LRNLWGPEQA TGLPLDVNVV ALLMNRTDPK SLITHVCDL MSGARIHGLV FGDDTDQEAV AQMLDFISSQ TFIPILGIHG GASMIMADKD PTSTFFQFGA SIQQQATVML K IMQDYDWH ...String: MGRLGYWTLL VLPALLVWRD PAQNAAAEKG PPALNIAVLL GHSHDVTERE LRNLWGPEQA TGLPLDVNVV ALLMNRTDPK SLITHVCDL MSGARIHGLV FGDDTDQEAV AQMLDFISSQ TFIPILGIHG GASMIMADKD PTSTFFQFGA SIQQQATVML K IMQDYDWH VFSLVTTIFP GYRDFISFIK TTVDNSFVGW DMQNVITLDT SFEDAKTQVQ LKKIHSSVIL LYCSKDEAVL IL SEARSLG LTGYDFFWIV PSLVSGNTEL IPKEFPSGLI SVSYDDWDYS LEARVRDGLG ILTTAASSML EKFSYIPEAK ASC YGQAEK PETPLHTLHQ FMVNVTWDGK DLSFTEEGYQ VHPRLVVIVL NKDREWEKVG KWENQTLSLR HAVWPRYKSF SDCE PDDNH LSIVTLEEAP FVIVEDIDPL TETCVRNTVP CRKFVKINNS TNEGMNVKKC CKGFCIDILK KLSRTVKFTY DLYLV TNGK HGKKVNNVWN GMIGEVVYQR AVMAVGSLTI NEERSEVVDF SVPFVETGIS VMVSRSNGTV SPSAFLEPFS ASVWVM MFV MLLIVSAIAV FVFEYFSPVG YNRNLAKGKA PHGPSFTIGK AIWLLWGLVF NNSVPVQNPK GTTSKIMVSV WAFFAVI FL ASYTANLAAF MIQEEFVDQV TGLSDKKFQR PHDYSPPFRF GTVPNGSTER NIRNNYPYMH QYMTRFNQRG VEDALVSL K TGKLDAFIYD AAVLNYKAGR DEGCKLVTIG SGYIFATTGY GIALQKGSPW KRQIDLALLQ FVGDGEMEEL ETLWLTGIC HNEKNEVMSS QLDIDNMAGV FYMLAAAMAL SLITFIW |
-Macromolecule #3: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 3 / Number of copies: 34 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 4.0 mg/mL | |||||||||||||||
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Buffer | pH: 7.4 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: AIR | |||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 291 K / Instrument: FEI VITROBOT MARK IV Details: sample was blotted for 3 seconds at blot force 1.. | |||||||||||||||
Details | This sample was monodisperse |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm |
Image recording | Film or detector model: GATAN K2 BASE (4k x 4k) / Number grids imaged: 2 / Number real images: 1068 / Average exposure time: 22.0 sec. / Average electron dose: 52.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
CTF correction | Software - Name: Gctf |
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Startup model | Type of model: NONE Details: Cleaned-up particles were used in CryoSPARC for de novo model generation. |
Initial angle assignment | Type: RANDOM ASSIGNMENT / Software - Name: RELION |
Final 3D classification | Software - Name: RELION |
Final angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: RELION |
Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Algorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 8.21 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cisTEM / Number images used: 23049 |
-Atomic model buiding 1
Initial model |
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Refinement | Protocol: RIGID BODY FIT | ||||||||||
Output model | PDB-6mmh: |