+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-42522 | |||||||||||||||
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Title | Glycine-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 / excitatory chemical synaptic transmission / Synaptic adhesion-like molecules / propylene metabolic process / response to glycine / glutamate-gated calcium ion channel activity / Assembly and cell surface presentation of NMDA receptors / regulation of monoatomic cation transmembrane transport / glutamate receptor activity / Neurexins and neuroligins ...negative regulation of dendritic spine development / excitatory chemical synaptic transmission / Synaptic adhesion-like molecules / propylene metabolic process / response to glycine / glutamate-gated calcium ion channel activity / Assembly and cell surface presentation of NMDA receptors / regulation of monoatomic cation transmembrane transport / glutamate receptor activity / Neurexins and neuroligins / NMDA glutamate receptor activity / NMDA selective glutamate receptor complex / calcium ion transmembrane import into cytosol / protein heterotetramerization / glutamate binding / positive regulation of reactive oxygen species biosynthetic process / glycine binding / positive regulation of calcium ion transport into cytosol / regulation of neuronal synaptic plasticity / Negative regulation of NMDA receptor-mediated neuronal transmission / dendrite development / Unblocking of NMDA receptors, glutamate binding and activation / monoatomic cation transmembrane transport / positive regulation of excitatory postsynaptic potential / ligand-gated monoatomic ion channel activity / Long-term potentiation / monoatomic cation transport / excitatory synapse / calcium ion homeostasis / synaptic cleft / prepulse inhibition / EPHB-mediated forward signaling / excitatory postsynaptic potential / presynaptic modulation of chemical synaptic transmission / ionotropic glutamate receptor signaling pathway / Ras activation upon Ca2+ influx through NMDA receptor / regulation of membrane potential / positive regulation of synaptic transmission, glutamatergic / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / protein phosphatase 2A binding / synaptic membrane / synaptic transmission, glutamatergic / postsynaptic density membrane / brain development / regulation of synaptic plasticity / modulation of chemical synaptic transmission / calcium channel activity / visual learning / terminal bouton / rhythmic process / calcium ion transport / synaptic vesicle / presynapse / signaling receptor activity / amyloid-beta binding / chemical synaptic transmission / RAF/MAP kinase cascade / postsynaptic membrane / response to ethanol / dendritic spine / postsynaptic density / calmodulin binding / neuron projection / dendrite / neuronal cell body / glutamatergic synapse / synapse / calcium ion binding / protein-containing complex binding / endoplasmic reticulum membrane / cell surface / positive regulation of transcription by RNA polymerase II / membrane / identical protein binding / plasma membrane / cytoplasm Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.1 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_42522.map.gz | 229.8 MB | EMDB map data format | |
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Header (meta data) | emd-42522-v30.xml emd-42522.xml | 16.1 KB 16.1 KB | Display Display | EMDB header |
Images | emd_42522.png | 99.1 KB | ||
Filedesc metadata | emd-42522.cif.gz | 6.2 KB | ||
Others | emd_42522_half_map_1.map.gz emd_42522_half_map_2.map.gz | 226.1 MB 226.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-42522 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-42522 | HTTPS FTP |
-Related structure data
Related structure data | 8usxMC 8uswC 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_42522.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: #2
File | emd_42522_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_42522_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Glycine-bound GluN1-3A NMDA receptor
Entire | Name: Glycine-bound GluN1-3A NMDA receptor |
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Components |
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-Supramolecule #1: Glycine-bound GluN1-3A NMDA receptor
Supramolecule | Name: Glycine-bound GluN1-3A NMDA receptor / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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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: 95.055695 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 AFLVLDRPEE 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 |
-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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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.8 µm |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: NONE |
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Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: RANDOM ASSIGNMENT |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 225900 |