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Yorodumi- EMDB-27961: Human GluN1a-GluN2A-GluN2C triheteromeric NMDA receptor in comple... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-27961 | |||||||||
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Title | Human GluN1a-GluN2A-GluN2C triheteromeric NMDA receptor in complex with Nb-4 | |||||||||
Map data | B-factor sharpened map | |||||||||
Sample |
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Function / homology | Function and homology information excitatory chemical synaptic transmission / directional locomotion / Synaptic adhesion-like molecules / serotonin metabolic process / protein localization to postsynaptic membrane / propylene metabolic process / response to glycine / sleep / activation of cysteine-type endopeptidase activity / regulation of monoatomic cation transmembrane transport ...excitatory chemical synaptic transmission / directional locomotion / Synaptic adhesion-like molecules / serotonin metabolic process / protein localization to postsynaptic membrane / propylene metabolic process / response to glycine / sleep / activation of cysteine-type endopeptidase activity / regulation of monoatomic cation transmembrane transport / Assembly and cell surface presentation of NMDA receptors / glutamate receptor signaling pathway / 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 / dopamine metabolic process / 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 / neuromuscular process controlling balance / excitatory synapse / neurogenesis / positive regulation of synaptic transmission, glutamatergic / calcium ion homeostasis / synaptic cleft / MECP2 regulates neuronal receptors and channels / glutamate-gated calcium ion channel activity / sensory perception of pain / EPHB-mediated forward signaling / response to amphetamine / Ras activation upon Ca2+ influx through NMDA receptor / ionotropic glutamate receptor signaling pathway / regulation of membrane potential / excitatory postsynaptic potential / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / synaptic membrane / synaptic transmission, glutamatergic / negative regulation of protein catabolic process / long-term synaptic potentiation / postsynaptic density membrane / visual learning / cytoplasmic vesicle membrane / protein catabolic process / brain development / regulation of synaptic plasticity / terminal bouton / memory / response to wounding / synaptic vesicle / signaling receptor activity / presynaptic membrane / RAF/MAP kinase cascade / amyloid-beta binding / chemical synaptic transmission / postsynaptic membrane / response to ethanol / learning or memory / dendritic spine / calmodulin binding / postsynaptic density / neuron projection / response to xenobiotic stimulus / positive regulation of apoptotic process / glutamatergic synapse / synapse / dendrite / calcium ion binding / endoplasmic reticulum membrane / protein-containing complex binding / cell surface / positive regulation of transcription by RNA polymerase II / zinc ion binding / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Lama glama (llama) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.24 Å | |||||||||
Authors | Chou T-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_27961.map.gz | 226.9 MB | EMDB map data format | |
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Header (meta data) | emd-27961-v30.xml emd-27961.xml | 21.4 KB 21.4 KB | Display Display | EMDB header |
Images | emd_27961.png | 32.3 KB | ||
Others | emd_27961_half_map_1.map.gz emd_27961_half_map_2.map.gz | 59.1 MB 59.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-27961 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-27961 | HTTPS FTP |
-Validation report
Summary document | emd_27961_validation.pdf.gz | 752.5 KB | Display | EMDB validaton report |
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Full document | emd_27961_full_validation.pdf.gz | 752.1 KB | Display | |
Data in XML | emd_27961_validation.xml.gz | 16.4 KB | Display | |
Data in CIF | emd_27961_validation.cif.gz | 19.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27961 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27961 | HTTPS FTP |
-Related structure data
Related structure data | 8e99MC 8e92C 8e93C 8e94C 8e96C 8e97C 8e98C 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_27961.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 | ||||||||||||||||||||
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: Half map 1
File | emd_27961_half_map_1.map | ||||||||||||
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Annotation | Half map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map 2
File | emd_27961_half_map_2.map | ||||||||||||
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Annotation | Half map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Hetero-tetrameric GluN1a-GluN2C NMDA receptors
Entire | Name: Hetero-tetrameric GluN1a-GluN2C NMDA receptors |
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Components |
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-Supramolecule #1: Hetero-tetrameric GluN1a-GluN2C NMDA receptors
Supramolecule | Name: Hetero-tetrameric GluN1a-GluN2C NMDA receptors / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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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: 95.081688 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 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 KDANGAQ |
-Macromolecule #2: Glutamate receptor ionotropic, NMDA 2A
Macromolecule | Name: Glutamate receptor ionotropic, NMDA 2A / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 97.770867 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: GSGATNFSLL KQAGDVEENP GPMGTMRLFL LAVLFLFSFA RATGGPPALN IAVMLGHSHD VTERELRTLW GPEQAAGLPL DVNVVALLM NRTDPKSLIT HVCDLMSGAR IHGLVFGDDT DQEAVAQMLD FISSHTFVPI LGIHGGASMI MADKDPTSTF F QFGASIQQ ...String: GSGATNFSLL KQAGDVEENP GPMGTMRLFL LAVLFLFSFA RATGGPPALN IAVMLGHSHD VTERELRTLW GPEQAAGLPL DVNVVALLM NRTDPKSLIT HVCDLMSGAR IHGLVFGDDT DQEAVAQMLD FISSHTFVPI LGIHGGASMI MADKDPTSTF F QFGASIQQ QATVMLKIMQ DYDWHVFSLV TTIFPGYREF ISFVKTTVDN SFVGWDMQNV ITLDTSFEDA KTQVQLKKIH SS VILLYSS KDEAVLILSE ARSLGLTGYD FFWIVPSLVS GNTELIPKEF PSGLISVSYD DWDYSLEARV RDGIGILTTA ASS MLEKFS YIPEAKASCY GQMERPEVPM HTLHPFMVNV TWDGKDLSFT EEGYQVHPRL VVIVLNKDRE WEKVGKWENH TLSL RHAVW PRYKSFSDSE PDDNHLSIVT LEEAPFVIVE DIDPLTETCV RNTVPCRKFV KINNSTNEGM NVKKCCKGFS IDILK KLSR TVKFTYDLYL VTNGKHGKKV NNVWNGMIGE VVYQRAVMAV GSLTINEERS EVVDFSVPFV ETGISVMVSR SNGTVS PSA FLEPFSASVW VMMFVMLLIV SAIAVFVFEY FSPVGYNRNL AKGKAPHGPS FTIGKAIWLL WGLVFNNSVP VQNPKGT TS KIMVSVWAFF AVIFLASYTA NLAAFMIQEE FVDQVTGLSD KKFQRPHDYS PPFRFGTVPN GSTERNIRNN YPYMHQYM T KFNQKGVEDA LVSLKTGKLD AFIYDAAVLN YKAGRDEGCK LVTIGSGYIF ATTGYGIALQ KGSPWKRQID LALLQFVGD GEMEELETLW LTGICHNEKN EVMSSQLDID NMAGVFYMLA AAMALSLITF IWEHLFYWKL RFSFTGTETS QVAPA |
-Macromolecule #3: Glutamate receptor ionotropic, NMDA 2C
Macromolecule | Name: Glutamate receptor ionotropic, NMDA 2C / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 96.958406 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MGTMRLFLLA VLFLFSFARA TGWSHPQFEK GGGSGGGSGG SAWSHPQFEK GALVPRGEQG MTVAVVFSSS GPPQAQFRAR LTPQSFLDL PLEIQPLTVG VNTTNPSSLL TQICGLLGAA HVHGIVFEDN VDTEAVAQIL DFISSQTHVP ILSISGGSAV V LTPKEPGS ...String: MGTMRLFLLA VLFLFSFARA TGWSHPQFEK GGGSGGGSGG SAWSHPQFEK GALVPRGEQG MTVAVVFSSS GPPQAQFRAR LTPQSFLDL PLEIQPLTVG VNTTNPSSLL TQICGLLGAA HVHGIVFEDN VDTEAVAQIL DFISSQTHVP ILSISGGSAV V LTPKEPGS AFLQLGVSLE QQLQVLFKVL EEYDWSAFAV ITSLHPGHAL FLEGVRAVAD ASHVSWRLLD VVTLELGPGG PR ARTQRLL RQLDAPVFVA YCSREEAEVL FAEAAQAGLV GPGHVWLVPN LALGSTDAPP ATFPVGLISV VTESWRLSLR QKV RDGVAI LALGAHSYWR QHGTLPAPAG DCRVHPGPVS PAREAFYRHL LNVTWEGRDF SFSPGGYLVQ PTMVVIALNR HRLW EMVGR WEHGVLYMKY PVWPRYSASL QPVVDSRHLT VATLEERPFV IVESPDPGTG GCVPNTVPCR RQSNHTFSSG DVAPY TKLC CKGFCIDILK KLARVVKFSY DLYLVTNGKH GKRVRGVWNG MIGEVYYKRA DMAIGSLTIN EERSEIVDFS VPFVET GIS VMVARSNGTV SPSAFLEPYS PAVWVMMFVM CLTVVAITVF MFEYFSPVSY NQNLTRGKKS GGPAFTIGKS VWLLWAL VF NNSVPIENPR GTTSKIMVLV WAFFAVIFLA SYTANLAAFM IQEQYIDTVS GLSDKKFQRP QDQYPPFRFG TVPNGSTE R NIRSNYRDMH THMVKFNQRS VEDALTSLKM GKLDAFIYDA AVLNYMAGKD EGCKLVTIGS GKVFATTGYG IAMQKDSHW KRAIDLALLQ FLGDGETQKL ETVWLSGICQ NEKNEVMSSK LDIDNMAGVF YMLLVAMGLA LLVFAWEHLV YWKLRHSVPN |
-Macromolecule #4: Nanobody 4
Macromolecule | Name: Nanobody 4 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Lama glama (llama) |
Molecular weight | Theoretical: 16.549539 KDa |
Recombinant expression | Organism: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) |
Sequence | String: MKYLLPTAAA GLLLLAAQPA MAQVQLQESG GGLVQAGGSL RLSCAASAAA AAAAAAGWYR QAPGKERAAA AAAAAAAAAA AADSVKGRF TISRDNAKNT VYLQMNSLKP EDTAVYYCAA AAAAAAAAAY WGQGTQVTVS SGSGSSRLEE ELRRRLTEHH H HHH |
-Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 2 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-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 |
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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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 57.6 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 |
-Image processing
Startup model | Type of model: EMDB MAP EMDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 4.24 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cisTEM (ver. 1.0.2) / Number images used: 375086 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |