+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-27957 | |||||||||
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Title | Glycine and glutamate bound Human GluN1a-GluN2D NMDA receptor | |||||||||
Map data | Composite map | |||||||||
Sample |
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Function / homology | Function and homology information excitatory chemical synaptic transmission / regulation of sensory perception of pain / Synaptic adhesion-like molecules / cellular response to L-glutamate / propylene metabolic process / response to glycine / regulation of monoatomic cation transmembrane transport / voltage-gated monoatomic cation channel activity / Assembly and cell surface presentation of NMDA receptors / NMDA glutamate receptor activity ...excitatory chemical synaptic transmission / regulation of sensory perception of pain / Synaptic adhesion-like molecules / cellular response to L-glutamate / propylene metabolic process / response to glycine / regulation of monoatomic cation transmembrane transport / voltage-gated monoatomic cation channel activity / 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 / protein heterotetramerization / positive regulation of calcium ion transport into cytosol / positive regulation of reactive oxygen species biosynthetic process / glycine binding / 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 / Long-term potentiation / excitatory synapse / ligand-gated monoatomic ion channel activity / positive regulation of excitatory postsynaptic potential / calcium ion homeostasis / synaptic cleft / glutamate-gated receptor activity / glutamate-gated calcium ion channel activity / presynaptic active zone membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / EPHB-mediated forward signaling / 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 / regulation of membrane potential / excitatory postsynaptic potential / synaptic membrane / synaptic transmission, glutamatergic / long-term synaptic potentiation / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / postsynaptic density membrane / brain development / visual learning / regulation of synaptic plasticity / 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 / dendrite / calcium ion binding / synapse / 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 | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.38 Å | |||||||||
Authors | Kang H / Furukawa H | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Mol Cell / Year: 2022 Title: Structural insights into assembly and function of GluN1-2C, GluN1-2A-2C, and GluN1-2D NMDARs. Authors: Tsung-Han Chou / Hyunook Kang / Noriko Simorowski / Stephen F Traynelis / Hiro Furukawa / Abstract: Neurotransmission mediated by diverse subtypes of N-methyl-D-aspartate receptors (NMDARs) is fundamental for basic brain functions and development as well as neuropsychiatric diseases and disorders. ...Neurotransmission mediated by diverse subtypes of N-methyl-D-aspartate receptors (NMDARs) is fundamental for basic brain functions and development as well as neuropsychiatric diseases and disorders. NMDARs are glycine- and glutamate-gated ion channels that exist as heterotetramers composed of obligatory GluN1 and GluN2(A-D) and/or GluN3(A-B). The GluN2C and GluN2D subunits form ion channels with distinct properties and spatio-temporal expression patterns. Here, we provide the structures of the agonist-bound human GluN1-2C NMDAR in the presence and absence of the GluN2C-selective positive allosteric potentiator (PAM), PYD-106, the agonist-bound GluN1-2A-2C tri-heteromeric NMDAR, and agonist-bound GluN1-2D NMDARs by single-particle electron cryomicroscopy. Our analysis shows unique inter-subunit and domain arrangements of the GluN2C NMDARs, which contribute to functional regulation and formation of the PAM binding pocket and is distinct from GluN2D NMDARs. Our findings here provide the fundamental blueprint to study GluN2C- and GluN2D-containing NMDARs, which are uniquely involved in neuropsychiatric disorders. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_27957.map.gz | 227.5 MB | EMDB map data format | |
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Header (meta data) | emd-27957-v30.xml emd-27957.xml | 23.9 KB 23.9 KB | Display Display | EMDB header |
Images | emd_27957.png | 75 KB | ||
Others | emd_27957_additional_1.map.gz emd_27957_additional_2.map.gz emd_27957_additional_3.map.gz | 229.9 MB 230.2 MB 229.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-27957 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-27957 | HTTPS FTP |
-Validation report
Summary document | emd_27957_validation.pdf.gz | 422.2 KB | Display | EMDB validaton report |
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Full document | emd_27957_full_validation.pdf.gz | 421.8 KB | Display | |
Data in XML | emd_27957_validation.xml.gz | 7.1 KB | Display | |
Data in CIF | emd_27957_validation.cif.gz | 8.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27957 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27957 | HTTPS FTP |
-Related structure data
Related structure data | 8e96MC 8e92C 8e93C 8e94C 8e97C 8e98C 8e99C C: citing same article (ref.) M: atomic model generated by this map |
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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_27957.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | Composite map | ||||||||||||||||||||||||||||||||||||
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
-Additional map: ECD Local
File | emd_27957_additional_1.map | ||||||||||||
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Annotation | ECD_Local | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: LBD Local
File | emd_27957_additional_2.map | ||||||||||||
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Annotation | LBD_Local | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: TMD Local
File | emd_27957_additional_3.map | ||||||||||||
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Annotation | TMD_Local | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Hetero-tetrameric GluN1a-GluN2D NMDA receptors
Entire | Name: Hetero-tetrameric GluN1a-GluN2D NMDA receptors |
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Components |
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-Supramolecule #1: Hetero-tetrameric GluN1a-GluN2D NMDA receptors
Supramolecule | Name: Hetero-tetrameric GluN1a-GluN2D NMDA receptors / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Homo sapiens (human) |
-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: 93.07825 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: RAASDPKIVN IGAVLSTRKH EQMFREAVNQ ANKRHGSWKI QLNATSVTHK PNAIQMALSV CEDLISSQVY AILVSHPPTP NDHFTPTPV SYTAGFYRIP VLGLTTRMSI YSDKSIHLSF LRTVPPYSHQ SSVWFEMMRV YSWNHIILLV SDDHEGRAAQ K RLETLLEE ...String: RAASDPKIVN IGAVLSTRKH EQMFREAVNQ ANKRHGSWKI QLNATSVTHK PNAIQMALSV CEDLISSQVY AILVSHPPTP NDHFTPTPV SYTAGFYRIP VLGLTTRMSI YSDKSIHLSF LRTVPPYSHQ SSVWFEMMRV YSWNHIILLV SDDHEGRAAQ K RLETLLEE RESKAEKVLQ FDPGTKNVTA LLMEAKELEA RVIILSASED DAATVYRAAA MLNMTGSGYV WLVGEREISG NA LRYAPDG ILGLQLINGK NESAHISDAV GVVAQAVHEL LEKENITDPP RGCVGNTNIW KTGPLFKRVL MSSKYADGVT GRV EFNEDG DRKFANYSIM NLQNRKLVQV GIYNGTHVIP NDRKIIWPGG ETEKPRGYQM STRLKIVTIH QEPFVYVKPT LSDG TCKEE FTVNGDPVKK VICTGPNDTS PGSPRHTVPQ CCYGFCIDLL IKLARTMNFT YEVHLVADGK FGTQERVNNS NKKEW NGMM GELLSGQADM IVAPLTINNE RAQYIEFSKP FKYQGLTILV KKEIPRSTLD SFMQPFQSTL WLLVGLSVHV VAVMLY LLD RFSPFGRFKV NSEEEEEDAL TLSSAMWFSW GVLLNSGIGE GAPRSFSARI LGMVWAGFAM IIVASYTANL AAFLVLD RP EERITGINDP RLRNPSDKFI YATVKQSSVD IYFRRQVELS TMYRHMEKHN YESAAEAIQA VRDNKLHAFI WDSAVLEF E ASQKCDLVTT GELFFRSGFG IGMRKDSPWK QNVSLSILKS HENGFMEDLD KTWVRYQECD SRSNAPATLT FENMAGVFM LVAGGIVAGI FLIFIEIAYK RHKDANGAQ |
-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: Homo sapiens (human) |
Molecular weight | Theoretical: 96.760492 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: WSHPQFEKGG GSGGGSGGSA WSHPQFEKGA LVPRGFPEEA PGPGGAGGPG GGLGGARPLN VALVFSGPAY AAEAARLGPA VAAAVRSPG LDVRPVALVL NGSDPRSLVL QLCDLLSGLR VHGVVFEDDS RAPAVAPILD FLSAQTSLPI VAVHGGAALV L TPKEKGST ...String: WSHPQFEKGG GSGGGSGGSA WSHPQFEKGA LVPRGFPEEA PGPGGAGGPG GGLGGARPLN VALVFSGPAY AAEAARLGPA VAAAVRSPG LDVRPVALVL NGSDPRSLVL QLCDLLSGLR VHGVVFEDDS RAPAVAPILD FLSAQTSLPI VAVHGGAALV L TPKEKGST FLQLGSSTEQ QLQVIFEVLE EYDWTSFVAV TTRAPGHRAF LSYIEVLTDG SLVGWEHRGA LTLDPGAGEA VL SAQLRSV SAQIRLLFCA REEAEPVFRA AEEAGLTGSG YVWFMVGPQL AGGGGSGAPG EPPLLPGGAP LPAGLFAVRS AGW RDDLAR RVAAGVAVVA RGAQALLRDY GFLPELGHDC RAQNRTHRGE SLHRYFMNIT WDNRDYSFNE DGFLVNPSLV VISL TRDRT WEVVGSWEQQ TLRLKYPLWS RYGRFLQPVD DTQHLTVATL EERPFVIVEP ADPISGTCIR DSVPCRSQLN RTHSP PPDA PRPEKRCCKG FCIDILKRLA HTIGFSYDLY LVTNGKHGKK IDGVWNGMIG EVFYQRADMA IGSLTINEER SEIVDF SVP FVETGISVMV ARSNGTVSPS AFLEPYSPAV WVMMFVMCLT VVAVTVFIFE YLSPVGYNRS LATGKRPGGS TFTIGKS IW LLWALVFNNS VPVENPRGTT SKIMVLVWAF FAVIFLASYT ANLAAFMIQE EYVDTVSGLS DRKFQRPQEQ YPPLKFGT V PNGSTEKNIR SNYPDMHSYM VRYNQPRVEE ALTQLKAGKL DAFIYDAAVL NYMARKDEGC KLVTIGSGKV FATTGYGIA LHKGSRWKRP IDLALLQFLG DDEIEMLERL WLSGICHNDK IEVMSSKLDI DNMAGVFYML LVAMGLSLLV FAWEHLVYWR LRHCLGP |
-Macromolecule #3: GLYCINE
Macromolecule | Name: GLYCINE / type: ligand / ID: 3 / Number of copies: 2 / Formula: GLY |
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Molecular weight | Theoretical: 75.067 Da |
Chemical component information | ChemComp-GLY: |
-Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 6 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Macromolecule #5: GLUTAMIC ACID
Macromolecule | Name: GLUTAMIC ACID / type: ligand / ID: 5 / 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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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 4 mg/mL |
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Buffer | pH: 7.5 |
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 85 % / Chamber temperature: 285 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 74.7 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.4 µm / Nominal defocus min: 0.6 µm |
Sample stage | Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |