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- EMDB-33792: Structure of GluN1a-GluN2D NMDA receptor in complex with agonists... -
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Open data
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Basic information
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Title | Structure of GluN1a-GluN2D NMDA receptor in complex with agonists glycine and glutamate. | ||||||||||||||||||
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![]() | ion channel / cryo-EM structure / glutamate receptor / synaptic protein / ELECTRON TRANSPORT | ||||||||||||||||||
Function / homology | ![]() excitatory chemical synaptic transmission / regulation of sensory perception of pain / cellular response to L-glutamate / Synaptic adhesion-like molecules / propylene metabolic process / response to glycine / voltage-gated monoatomic cation channel activity / regulation of monoatomic cation transmembrane transport / Assembly and cell surface presentation of NMDA receptors / NMDA glutamate receptor activity ...excitatory chemical synaptic transmission / regulation of sensory perception of pain / cellular response to L-glutamate / Synaptic adhesion-like molecules / propylene metabolic process / response to glycine / voltage-gated monoatomic cation channel activity / regulation of monoatomic cation transmembrane transport / Assembly and cell surface presentation of NMDA receptors / NMDA glutamate receptor activity / Neurexins and neuroligins / NMDA selective glutamate receptor complex / calcium ion transmembrane import into cytosol / glutamate binding / positive regulation of reactive oxygen species biosynthetic process / protein heterotetramerization / glycine binding / positive regulation of calcium ion transport into cytosol / Negative regulation of NMDA receptor-mediated neuronal transmission / Unblocking of NMDA receptors, glutamate binding and activation / startle response / regulation of neuronal synaptic plasticity / monoatomic cation transmembrane transport / monoatomic cation transport / positive regulation of excitatory postsynaptic potential / Long-term potentiation / ligand-gated monoatomic ion channel activity / excitatory synapse / calcium ion homeostasis / synaptic cleft / glutamate-gated calcium ion channel activity / glutamate-gated receptor activity / presynaptic active zone membrane / EPHB-mediated forward signaling / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / Ras activation upon Ca2+ influx through NMDA receptor / ionotropic glutamate receptor signaling pathway / hippocampal mossy fiber to CA3 synapse / positive regulation of synaptic transmission, glutamatergic / adult locomotory behavior / excitatory postsynaptic potential / regulation of membrane potential / synaptic membrane / synaptic transmission, glutamatergic / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / long-term synaptic potentiation / postsynaptic density membrane / visual learning / regulation of synaptic plasticity / brain development / terminal bouton / synaptic vesicle / signaling receptor activity / amyloid-beta binding / RAF/MAP kinase cascade / chemical synaptic transmission / postsynaptic membrane / response to ethanol / dendritic spine / postsynaptic density / calmodulin binding / neuron projection / glutamatergic synapse / synapse / dendrite / calcium ion binding / endoplasmic reticulum membrane / protein-containing complex binding / cell surface / positive regulation of transcription by RNA polymerase II / plasma membrane / cytoplasm Similarity search - Function | ||||||||||||||||||
Biological species | ![]() | ||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | ||||||||||||||||||
![]() | Zhang JL / Zhu SJ / Zhang M | ||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Distinct structure and gating mechanism in diverse NMDA receptors with GluN2C and GluN2D subunits. Authors: Jilin Zhang / Ming Zhang / Qinrui Wang / Han Wen / Zheyi Liu / Fangjun Wang / Yuhang Wang / Fenyong Yao / Nan Song / Zengwei Kou / Yang Li / Fei Guo / Shujia Zhu / ![]() Abstract: N-methyl-D-aspartate (NMDA) receptors are heterotetramers comprising two GluN1 and two alternate GluN2 (N2A-N2D) subunits. Here we report full-length cryo-EM structures of the human N1-N2D di- ...N-methyl-D-aspartate (NMDA) receptors are heterotetramers comprising two GluN1 and two alternate GluN2 (N2A-N2D) subunits. Here we report full-length cryo-EM structures of the human N1-N2D di-heterotetramer (di-receptor), rat N1-N2C di-receptor and N1-N2A-N2C tri-heterotetramer (tri-receptor) at a best resolution of 3.0 Å. The bilobate N-terminal domain (NTD) in N2D intrinsically adopts a closed conformation, leading to a compact NTD tetramer in the N1-N2D receptor. Additionally, crosslinking the ligand-binding domain (LBD) of two N1 protomers significantly elevated the channel open probability (Po) in N1-N2D di-receptors. Surprisingly, the N1-N2C di-receptor adopted both symmetric (minor) and asymmetric (major) conformations, the latter further locked by an allosteric potentiator, PYD-106, binding to a pocket between the NTD and LBD in only one N2C protomer. Finally, the N2A and N2C subunits in the N1-N2A-N2C tri-receptor display a conformation close to one protomer in the N1-N2A and N1-N2C di-receptors, respectively. These findings provide a comprehensive structural understanding of diverse function in major NMDA receptor subtypes. | ||||||||||||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 34.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 21.8 KB 21.8 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.3 KB | Display | ![]() |
Images | ![]() | 38.7 KB | ||
Masks | ![]() | 67 MB | ![]() | |
Others | ![]() ![]() | 61.8 MB 61.8 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7yflMC ![]() 7yffC ![]() 7yfgC ![]() 7yfhC ![]() 7yfiC ![]() 7yfmC ![]() 7yfoC ![]() 7yfrC ![]() 8hdkC C: citing same article ( M: atomic model generated by this map |
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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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Voxel size | X=Y=Z: 1.06 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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-Half map: #2
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-Half map: #1
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Sample components
-Entire : NMDA receptor with NMDA 1 incorperated with NMDA 2D
Entire | Name: NMDA receptor with NMDA 1 incorperated with NMDA 2D |
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Components |
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-Supramolecule #1: NMDA receptor with NMDA 1 incorperated with NMDA 2D
Supramolecule | Name: NMDA receptor with NMDA 1 incorperated with NMDA 2D / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 384.54 kDa/nm |
-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: ![]() |
Molecular weight | Theoretical: 95.236078 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MSTMRLLTLA LLFSCSVARA ACDPKIVNIG AVLSTRKHEQ MFREAVNQAN KRHGSWKIQL NATSVTHKPN AIQMALSVCE DLISSQVYA ILVSHPPTPN DHFTPTPVSY TAGFYRIPVL GLTTRMSIYS DKSIHLSFLR TVPPYSHQSS VWFEMMRVYS W NHIILLVS ...String: MSTMRLLTLA LLFSCSVARA ACDPKIVNIG AVLSTRKHEQ MFREAVNQAN KRHGSWKIQL NATSVTHKPN AIQMALSVCE DLISSQVYA ILVSHPPTPN DHFTPTPVSY TAGFYRIPVL GLTTRMSIYS DKSIHLSFLR TVPPYSHQSS VWFEMMRVYS W NHIILLVS DDHEGRAAQK RLETLLEERE SKAEKVLQFD PGTKNVTALL MEAKELEARV IILSASEDDA ATVYRAAAML NM TGSGYVW LVGEREISGN ALRYAPDGIL GLQLINGKNE SAHISDAVGV VAQAVHELLE KENITDPPRG CVGNTNIWKT GPL FKRVLM SSKYADGVTG RVEFNEDGDR KFANYSIMNL QNRKLVQVGI YNGTHVIPND RKIIWPGGET EKPRGYQMST RLKI VTIHQ EPFVYVKPTL 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 IFIEIAYKRH KDARRKQ UniProtKB: Glutamate receptor ionotropic, NMDA 1 |
-Macromolecule #2: Glutamate receptor ionotropic, NMDA 2D
Macromolecule | Name: Glutamate receptor ionotropic, NMDA 2D / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 97.226414 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MRGAGGPRGP RGPAKMLLLL ALACASPFPE EAPGPGGAGG PGGGLGGARP LNVALVFSGP AYAAEAARLG PAVAAAVRSP GLDVRPVAL VLNGSDPRSL VLQLCDLLSG LRVHGVVFED DSRAPAVAPI LDFLSAQTSL PIVAVHGGAA LVLTPKEKGS T FLQLGSST ...String: MRGAGGPRGP RGPAKMLLLL ALACASPFPE EAPGPGGAGG PGGGLGGARP LNVALVFSGP AYAAEAARLG PAVAAAVRSP GLDVRPVAL VLNGSDPRSL VLQLCDLLSG LRVHGVVFED DSRAPAVAPI LDFLSAQTSL PIVAVHGGAA LVLTPKEKGS T FLQLGSST EQQLQVIFEV LEEYDWTSFV AVTTRAPGHR AFLSYIEVLT DGSLVGWEHR GALTLDPGAG EAVLSAQLRS VS AQIRLLF CAREEAEPVF RAAEEAGLTG SGYVWFMVGP QLAGGGGSGA PGEPPLLPGG APLPAGLFAV RSAGWRDDLA RRV AAGVAV VARGAQALLR DYGFLPELGH DCRAQNRTHR GESLHRYFMN ITWDNRDYSF NEDGFLVNPS LVVISLTRDR TWEV VGSWE QQTLRLKYPL WSRYGRFLQP VDDTQHLTVA TLEERPFVIV EPADPISGTC IRDSVPCRSQ LNRTHSPPPD APRPE KRCC KGFCIDILKR LAHTIGFSYD LYLVTNGKHG KKIDGVWNGM IGEVFYQRAD MAIGSLTINE ERSEIVDFSV PFVETG ISV MVARSNGTVS PSAFLEPYSP AVWVMMFVMC LTVVAVTVFI FEYLSPVGYN RSLATGKRPG GSTFTIGKSI WLLWALV FN NSVPVENPRG TTSKIMVLVW AFFAVIFLAS YTANLAAFMI QEEYVDTVSG LSDRKFQRPQ EQYPPLKFGT VPNGSTEK N IRSNYPDMHS YMVRYNQPRV EEALTQLKAG KLDAFIYDAA VLNYMARKDE GCKLVTIGSG KVFATTGYGI ALHKGSRWK RPIDLALLQF LGDDEIEMLE RLWLSGICHN DKIEVMSSKL DIDNMAGVFY MLLVAMGLSL LVFAWEHLVY WRLRHCLGPA ASAWSHPQF EK UniProtKB: Glutamate receptor ionotropic, NMDA 2D |
-Macromolecule #4: GLYCINE
Macromolecule | Name: GLYCINE / type: ligand / ID: 4 / Number of copies: 2 / Formula: GLY |
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Molecular weight | Theoretical: 75.067 Da |
Chemical component information | ![]() ChemComp-GLY: |
-Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 10 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Macromolecule #6: GLUTAMIC ACID
Macromolecule | Name: GLUTAMIC ACID / type: ligand / ID: 6 / Number of copies: 2 / Formula: GLU |
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Molecular weight | Theoretical: 147.129 Da |
Chemical component information | ![]() ChemComp-GLU: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 4.0 mg/mL |
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Buffer | pH: 8 |
Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec. / Pretreatment - Atmosphere: AIR / Pretreatment - Pressure: 101.325 kPa |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 281 K / Instrument: FEI VITROBOT MARK IV / Details: Blot for 3 seconds before plunging. |
Details | This sample was monodisperse |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: DIRECT ELECTRON DE-10 (5k x 4k) / Detector mode: SUPER-RESOLUTION / Digitization - Frames/image: 1-40 / Number grids imaged: 1 / Number real images: 3840 / 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: 2.5 µm / Nominal defocus min: 1.5 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Initial model | PDB ID: Chain - Source name: PDB / Chain - Initial model type: experimental model |
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Refinement | Space: REAL / Protocol: FLEXIBLE FIT / Overall B value: 220 / Target criteria: Correlation coefficient |
Output model | ![]() PDB-7yfl: |