+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-42520 | |||||||||||||||
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Title | CNQX-bound GluN1a-3A NMDA receptor | |||||||||||||||
Map data | ||||||||||||||||
Sample |
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Keywords | Channel / receptor / MEMBRANE PROTEIN | |||||||||||||||
Function / homology | Function and homology information negative regulation of dendritic spine development / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / olfactory learning / dendritic branch / conditioned taste aversion / regulation of respiratory gaseous exchange ...negative regulation of dendritic spine development / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / olfactory learning / dendritic branch / conditioned taste aversion / regulation of respiratory gaseous exchange / protein localization to postsynaptic membrane / propylene metabolic process / response to glycine / glutamate receptor activity / regulation of monoatomic cation transmembrane transport / voltage-gated monoatomic cation channel activity / Assembly and cell surface presentation of NMDA receptors / Synaptic adhesion-like molecules / RAF/MAP kinase cascade / NMDA glutamate receptor activity / parallel fiber to Purkinje cell synapse / NMDA selective glutamate receptor complex / response to morphine / calcium ion transmembrane import into cytosol / glutamate binding / neuromuscular process / protein heterotetramerization / positive regulation of calcium ion transport into cytosol / positive regulation of reactive oxygen species biosynthetic process / regulation of synapse assembly / glycine binding / regulation of axonogenesis / regulation of dendrite morphogenesis / male mating behavior / suckling behavior / startle response / response to amine / dendrite development / regulation of neuronal synaptic plasticity / monoatomic cation transmembrane transport / associative learning / monoatomic cation transport / social behavior / excitatory synapse / ligand-gated monoatomic ion channel activity / positive regulation of excitatory postsynaptic potential / cellular response to glycine / positive regulation of dendritic spine maintenance / Unblocking of NMDA receptors, glutamate binding and activation / cellular response to manganese ion / phosphatase binding / glutamate receptor binding / long-term memory / regulation of neuron apoptotic process / monoatomic cation channel activity / prepulse inhibition / calcium ion homeostasis / synaptic cleft / glutamate-gated receptor activity / response to fungicide / glutamate-gated calcium ion channel activity / presynaptic active zone membrane / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / sensory perception of pain / presynaptic modulation of chemical synaptic transmission / response to amphetamine / ionotropic glutamate receptor signaling pathway / hippocampal mossy fiber to CA3 synapse / positive regulation of synaptic transmission, glutamatergic / adult locomotory behavior / regulation of membrane potential / excitatory postsynaptic potential / learning / protein phosphatase 2A binding / synaptic membrane / synaptic transmission, glutamatergic / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / postsynaptic density membrane / regulation of long-term neuronal synaptic plasticity / visual learning / modulation of chemical synaptic transmission / calcium channel activity / response to organic cyclic compound / regulation of synaptic plasticity / terminal bouton / cerebral cortex development / memory / intracellular calcium ion homeostasis / synaptic vesicle membrane / response to calcium ion / neuron cellular homeostasis / calcium ion transport / rhythmic process / synaptic vesicle / presynapse / signaling receptor activity / presynaptic membrane / amyloid-beta binding / protein-containing complex assembly Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.23 Å | |||||||||||||||
Authors | Michalski K / Furukawa H | |||||||||||||||
Funding support | United States, 4 items
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Citation | Journal: Sci Adv / Year: 2024 Title: Structure and function of GluN1-3A NMDA receptor excitatory glycine receptor channel. Authors: Kevin Michalski / Hiro Furukawa / Abstract: -methyl-d-aspartate receptors (NMDARs) and other ionotropic glutamate receptors (iGluRs) mediate most of the excitatory signaling in the mammalian brains in response to the neurotransmitter glutamate. ...-methyl-d-aspartate receptors (NMDARs) and other ionotropic glutamate receptors (iGluRs) mediate most of the excitatory signaling in the mammalian brains in response to the neurotransmitter glutamate. Uniquely, NMDARs composed of GluN1 and GluN3 are activated exclusively by glycine, the neurotransmitter conventionally mediating inhibitory signaling when it binds to pentameric glycine receptors. The GluN1-3 NMDARs are vital for regulating neuronal excitability, circuit function, and specific behaviors, yet our understanding of their functional mechanism at the molecular level has remained limited. Here, we present cryo-electron microscopy structures of GluN1-3A NMDARs bound to an antagonist, CNQX, and an agonist, glycine. The structures show a 1-3-1-3 subunit heterotetrameric arrangement and an unprecedented pattern of GluN3A subunit orientation shift between the glycine-bound and CNQX-bound structures. Site-directed disruption of the unique subunit interface in the glycine-bound structure mitigated desensitization. Our study provides a foundation for understanding the distinct structural dynamics of GluN3 that are linked to the unique function of GluN1-3 NMDARs. | |||||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_42520.map.gz | 230.1 MB | EMDB map data format | |
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Header (meta data) | emd-42520-v30.xml emd-42520.xml | 16.8 KB 16.8 KB | Display Display | EMDB header |
Images | emd_42520.png | 84.7 KB | ||
Filedesc metadata | emd-42520.cif.gz | 6.4 KB | ||
Others | emd_42520_half_map_1.map.gz emd_42520_half_map_2.map.gz | 226.6 MB 226.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-42520 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-42520 | HTTPS FTP |
-Validation report
Summary document | emd_42520_validation.pdf.gz | 856.6 KB | Display | EMDB validaton report |
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Full document | emd_42520_full_validation.pdf.gz | 856.1 KB | Display | |
Data in XML | emd_42520_validation.xml.gz | 15.8 KB | Display | |
Data in CIF | emd_42520_validation.cif.gz | 18.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-42520 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-42520 | HTTPS FTP |
-Related structure data
Related structure data | 8uswMC 8usxC 8uueC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_42520.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.856 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_42520_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_42520_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : CNQX-bound GluN1-3A NMDA receptor
Entire | Name: CNQX-bound GluN1-3A NMDA receptor |
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Components |
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-Supramolecule #1: CNQX-bound GluN1-3A NMDA receptor
Supramolecule | Name: CNQX-bound GluN1-3A NMDA receptor / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 400 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: Homo sapiens (human) |
Molecular weight | Theoretical: 95.041672 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MSTMHLLTFA LLFSCSFARA ASDPKIVNIG AVLSTRKHEQ MFREAVNQAN KRHGSWKIQL NATSVTHKPN AIQMALSVCE DLISSQVYA ILVSHPPTPN DHFTPTPVSY TAGFYRIPVL GLTTRMSIYS DKSIHLSFLR TVPPYSHQSS VWFEMMRVYS W NHIILLVS ...String: MSTMHLLTFA LLFSCSFARA ASDPKIVNIG 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 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 AFLVVDRPEE RITGINDPRL RNPSDKFIYA TVKQSSVDIY FRRQVELSTM YRHMEKHNYE SAAEAIQA V RDNKLHAFIW DSAVLEFEAS QKCDLVTTGE LFFRSGFGIG MRKDSPWKQN VSLSILKSHE NGFMEDLDKT WVRYQECDS RSNAPATLTC ENMAGVFMLV AGGIVAGIFL IFIEIAYKRH KDANGAQ UniProtKB: Glutamate receptor ionotropic, NMDA 1 |
-Macromolecule #2: Glutamate receptor ionotropic, NMDA 3A
Macromolecule | Name: Glutamate receptor ionotropic, NMDA 3A / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 104.837195 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: CQILKRIGHA VRVGAVHLQP WTTAPRAASR APDDSRAGAQ RDEPEPGTRR SPAPSPGARW LGSTLHGRGP PGSRKPGEGA RAEALWPRD ALLFAVDNLN RVEGLLPYNL SLEVVMAIEA GLGDLPLLPF SSPSSPWSSD PFSFLQSVCH TVVVQGVSAL L AFPQSQGE ...String: CQILKRIGHA VRVGAVHLQP WTTAPRAASR APDDSRAGAQ RDEPEPGTRR SPAPSPGARW LGSTLHGRGP PGSRKPGEGA RAEALWPRD ALLFAVDNLN RVEGLLPYNL SLEVVMAIEA GLGDLPLLPF SSPSSPWSSD PFSFLQSVCH TVVVQGVSAL L AFPQSQGE MMELDLVSLV LHIPVISIVR HEFPRESQNP LHLQLSLENS LSSDADVTVS ILTMNNWYNF SLLLCQEDWN IT DFLLLTQ NNSKFHLGSI INITANLPST QDLLSFLQIQ LESIKNSTPT VVMFGCDMES IRRIFEITTQ FGVMPPELRW VLG DSQNVE ELRTEGLPLG LIAHGKTTQS VFEHYVQDAM ELVARAVATA TMIQPELALI PSTMNCMEVE TTNLTSGQYL SRFL ANTTF RGLSGSIRVK GSTIVSSENN FFIWNLQHDP MGKPMWTRLG SWQGGKIVMD YGIWPEQAQR HKTHFQHPSK LHLRV VTLI EHPFVFTREV DDEGLCPAGQ LCLDPMTNDS STLDSLFSSL HSSNDTVPIK FKKCCYGYCI DLLEKIAEDM NFDFDL YIV GDGKYGAWKN GHWTGLVGDL LRGTAHMAVT SFSINTARSQ VIDFTSPFFS TSLGILVRTR DTAAPIGAFM WPLHWCM WL GIFVALHITA VFLTLYEWKS PFGLTPKGRN RSKVFSFSSA LNICYALLFG RTVAIKPPKC WTGRFLMNLW AIFCMFCL S TYTANLAAVM VGEKIYEELS GIHDPKLHHP SQGFRFGTVR ESSAEDYVRQ SFPEMHEYMR RYNVPATPDG VEYLKNDPE KLDAFIMDKA LLDYEVSIDA DCKLLTVGKP FAIEGYGIGL PPNSPLTANI SELISQYKSH GFMDMLHDKW YRVVPCGKRS FAVTETLQM GIKHFSGLFV LLCIGFGLSI LTTIGEHIVY RLLLPRIKNK STETSQVAPA UniProtKB: Glutamate receptor ionotropic, NMDA 3A |
-Macromolecule #3: 7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-carbonitrile
Macromolecule | Name: 7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-carbonitrile type: ligand / ID: 3 / Number of copies: 2 / Formula: DQC |
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Molecular weight | Theoretical: 232.152 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: OTHER / Cs: 2.7 mm / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: NONE |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 4.23 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 264487 |
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: RANDOM ASSIGNMENT |