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Yorodumi- EMDB-44586: Rat GluN1-GluN2B NMDA receptor channel in complex with glycine, g... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-44586 | |||||||||
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Title | Rat GluN1-GluN2B NMDA receptor channel in complex with glycine, glutamate, and EU-1622-A, in open-channel conformation, C1 symmetry | |||||||||
Map data | B-factor sharpened map | |||||||||
Sample |
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Keywords | Ionotropic glutamate receptor / synaptic membrane protein / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information organelle / 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 / conditioned taste aversion / dendritic branch / regulation of respiratory gaseous exchange ...organelle / 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 / conditioned taste aversion / dendritic branch / regulation of respiratory gaseous exchange / protein localization to postsynaptic membrane / propylene metabolic process / response to glycine / voltage-gated monoatomic cation channel activity / regulation of monoatomic cation transmembrane transport / response to morphine / NMDA glutamate receptor activity / Synaptic adhesion-like molecules / RAF/MAP kinase cascade / parallel fiber to Purkinje cell synapse / NMDA selective glutamate receptor complex / calcium ion transmembrane import into cytosol / neuromuscular process / glutamate binding / protein heterotetramerization / positive regulation of reactive oxygen species biosynthetic process / regulation of synapse assembly / regulation of axonogenesis / regulation of dendrite morphogenesis / positive regulation of calcium ion transport into cytosol / male mating behavior / glycine binding / suckling behavior / startle response / response to amine / monoatomic cation transmembrane transport / regulation of neuronal synaptic plasticity / monoatomic cation transport / associative learning / positive regulation of excitatory postsynaptic potential / social behavior / ligand-gated monoatomic ion channel activity / cellular response to glycine / excitatory synapse / positive regulation of dendritic spine maintenance / Unblocking of NMDA receptors, glutamate binding and activation / phosphatase binding / cellular response to manganese ion / glutamate receptor binding / long-term memory / prepulse inhibition / monoatomic cation channel activity / calcium ion homeostasis / regulation of neuron apoptotic process / synaptic cleft / glutamate-gated receptor activity / response to fungicide / presynaptic active zone membrane / glutamate-gated calcium ion channel activity / sensory perception of pain / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / 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 / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / synaptic membrane / synaptic transmission, glutamatergic / postsynaptic density membrane / regulation of long-term neuronal synaptic plasticity / visual learning / calcium channel activity / regulation of synaptic plasticity / response to organic cyclic compound / terminal bouton / cerebral cortex development / memory / synaptic vesicle membrane / intracellular calcium ion homeostasis / response to calcium ion / neuron cellular homeostasis / calcium ion transport / rhythmic process / synaptic vesicle / signaling receptor activity / presynaptic membrane / amyloid-beta binding / protein-containing complex assembly / chemical synaptic transmission / postsynaptic membrane / response to ethanol / negative regulation of neuron apoptotic process / transcription by RNA polymerase II / dendritic spine / postsynaptic density Similarity search - Function | |||||||||
Biological species | Rattus norvegicus (Norway rat) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.81 Å | |||||||||
Authors | Chou T-H / Furukawa H | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Nature / Year: 2024 Title: Molecular mechanism of ligand gating and opening of NMDA receptor. Authors: Tsung-Han Chou / Max Epstein / Russell G Fritzemeier / Nicholas S Akins / Srinu Paladugu / Elijah Z Ullman / Dennis C Liotta / Stephen F Traynelis / Hiro Furukawa / Abstract: Glutamate transmission and activation of ionotropic glutamate receptors are the fundamental means by which neurons control their excitability and neuroplasticity. The N-methyl-D-aspartate receptor ...Glutamate transmission and activation of ionotropic glutamate receptors are the fundamental means by which neurons control their excitability and neuroplasticity. The N-methyl-D-aspartate receptor (NMDAR) is unique among all ligand-gated channels, requiring two ligands-glutamate and glycine-for activation. These receptors function as heterotetrameric ion channels, with the channel opening dependent on the simultaneous binding of glycine and glutamate to the extracellular ligand-binding domains (LBDs) of the GluN1 and GluN2 subunits, respectively. The exact molecular mechanism for channel gating by the two ligands has been unclear, particularly without structures representing the open channel and apo states. Here we show that the channel gate opening requires tension in the linker connecting the LBD and transmembrane domain (TMD) and rotation of the extracellular domain relative to the TMD. Using electron cryomicroscopy, we captured the structure of the GluN1-GluN2B (GluN1-2B) NMDAR in its open state bound to a positive allosteric modulator. This process rotates and bends the pore-forming helices in GluN1 and GluN2B, altering the symmetry of the TMD channel from pseudofourfold to twofold. Structures of GluN1-2B NMDAR in apo and single-liganded states showed that binding of either glycine or glutamate alone leads to distinct GluN1-2B dimer arrangements but insufficient tension in the LBD-TMD linker for channel opening. This mechanistic framework identifies a key determinant for channel gating and a potential pharmacological strategy for modulating NMDAR activity. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_44586.map.gz | 230.3 MB | EMDB map data format | |
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Header (meta data) | emd-44586-v30.xml emd-44586.xml | 21.3 KB 21.3 KB | Display Display | EMDB header |
Images | emd_44586.png | 35.6 KB | ||
Filedesc metadata | emd-44586.cif.gz | 7.1 KB | ||
Others | emd_44586_additional_1.map.gz emd_44586_half_map_1.map.gz emd_44586_half_map_2.map.gz | 230 MB 226.4 MB 226.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-44586 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-44586 | HTTPS FTP |
-Validation report
Summary document | emd_44586_validation.pdf.gz | 924.5 KB | Display | EMDB validaton report |
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Full document | emd_44586_full_validation.pdf.gz | 924.1 KB | Display | |
Data in XML | emd_44586_validation.xml.gz | 15.9 KB | Display | |
Data in CIF | emd_44586_validation.cif.gz | 18.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-44586 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-44586 | HTTPS FTP |
-Related structure data
Related structure data | 9bibMC 9areC 9arfC 9argC 9arhC 9ariC 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_44586.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | B-factor sharpened map | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.861 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: Local refined map focused on TMD
File | emd_44586_additional_1.map | ||||||||||||
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Annotation | Local refined map focused on TMD | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map B
File | emd_44586_half_map_1.map | ||||||||||||
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Annotation | Half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map A
File | emd_44586_half_map_2.map | ||||||||||||
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Annotation | Half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Di-heterotetrameric GluN1-GluN2B NMDA receptors
Entire | Name: Di-heterotetrameric GluN1-GluN2B NMDA receptors |
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Components |
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-Supramolecule #1: Di-heterotetrameric GluN1-GluN2B NMDA receptors
Supramolecule | Name: Di-heterotetrameric GluN1-GluN2B NMDA receptors / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
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: Rattus norvegicus (Norway rat) |
Molecular weight | Theoretical: 95.225883 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MSTMHLLTFA LLFSCSFARA ASDPKIVNIG AVLSTRKHEQ MFREAVNQAN KRHGSWKIQL QATSVTHKPN AIQMALSVCE DLISSQVYA ILVSHPPTPN DHFTPTPVSY TAGFYRIPVL GLTTRMSIYS DKSIHLSFLR TVPPYSHQSS VWFEMMRVYN W NHIILLVS ...String: MSTMHLLTFA LLFSCSFARA ASDPKIVNIG AVLSTRKHEQ MFREAVNQAN KRHGSWKIQL QATSVTHKPN AIQMALSVCE DLISSQVYA ILVSHPPTPN DHFTPTPVSY TAGFYRIPVL GLTTRMSIYS DKSIHLSFLR TVPPYSHQSS VWFEMMRVYN W NHIILLVS DDHEGRAAQK RLETLLEERE SKAEKVLQFD PGTKNVTALL MEARELEARV IILSASEDDA ATVYRAAAML DM TGSGYVW LVGEREISGN ALRYAPDGII GLQLINGKNE SAHISDAVGV VAQAVHELLE KENITDPPRG CVGNTNIWKT GPL FKRVLM SSKYADGVTG RVEFNEDGDR KFAQYSIMNL QNRKLVQVGI YNGTHVIPND RKIIWPGGET EKPRGYQMST RLKI VTIHQ EPFVYVKPTM SDGTCKEEFT VNGDPVKKVI CTGPNDTSPG SPRHTVPQCC YGFCIDLLIK LARTMQFTYE VHLVA DGKF GTQERVQNSN 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 MRKDSPWKQQ VSLSILKSHE NGFMEDLDKT WVRYQECDS RSNAPATLTF ENMAGVFMLV AGGIVAGIFL IFIEIAYKRH KDANGAQ UniProtKB: Glutamate receptor ionotropic, NMDA 1 |
-Macromolecule #2: Glutamate receptor
Macromolecule | Name: Glutamate receptor / 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: 98.888945 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MGTMRLFLLA VLFLFSFARA TGWSHPQFEK GGGSGGGSGG SAWSHPQFEK GALVPRGRSQ KSPPSIGIAV ILVGTSDEVA IKDAHEKDD FHHLSVVPRV ELVAMNETDP KSIITRICDL MSDRKIQGVV FADDTDQEAI AQILDFISAQ TLTPILGIHG G SSMIMADK ...String: MGTMRLFLLA VLFLFSFARA TGWSHPQFEK GGGSGGGSGG SAWSHPQFEK GALVPRGRSQ KSPPSIGIAV ILVGTSDEVA IKDAHEKDD FHHLSVVPRV ELVAMNETDP KSIITRICDL MSDRKIQGVV FADDTDQEAI AQILDFISAQ TLTPILGIHG G SSMIMADK DESSMFFQFG PSIEQQASVM LNIMEEYDWY IFSIVTTYFP GYQDFVNKIR STIENSFVGW ELEEVLLLDM SL DDGDSKI QNQLKKLQSP IILLYCTKEE ATYIFEVANS VGLTGYGYTW IVPSLVAGDT DTVPSEFPTG LISVSYDEWD YGL PARVRD GIAIITTAAS DMLSEHSFIP EPKSSCYNTH EKRIYQSNML NRYLINVTFE GRNLSFSEDG YQMHPKLVII LLNK ERKWE RVGKWKDKSL QMKYYVWPRM CPETEEQEDD HLSIVTLEEA PFVIVESVDP LSGTCMRNTV PCQKRIISEN KTDEE PGYI KKCCKGFCID ILKKISKSVK FTYDLYLVTN GKHGKKINGT WNGMIGEVVM KRAYMAVGSL TINEERSEVV DFSVPF IET GISVMVSRSN GTVSPSAFLE PFSADVWVMM FVMLLIVSAV AVFVFEYFSP VGYNRCLADG REPGGPSFTI GKAIWLL WG LVFNNSVPVQ NPKGTTSKIM VSVWAFFAVI FLASYTANLA AFMIQEEYVD QVSGLSDKKF QRPNDFSPPF RFGTVPNG S TERNIRNNYA EMHAYMGKFN QRGVDDALLS LKTGKLDAFI YDAAVLNYMA GRDEGCKLVT IGSGKVFAST GYGIAIQKD SGWKRQVDLA ILQLFGDGEM EELEALWLTG ICHNEKNEVM SSQLDIDNMA GVFYMLGAAM ALSLITFICE HLFYWQFRHS FMG UniProtKB: Glutamate receptor |
-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: GLUTAMIC ACID
Macromolecule | Name: GLUTAMIC ACID / type: ligand / ID: 4 / 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: UltrAuFoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: GOLD / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 35 sec. |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 85 % / Chamber temperature: 285 K |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 66.3 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: 2.8000000000000003 µm / Nominal defocus min: 1.4000000000000001 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |