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- EMDB-27955: PYD-106-bound Human GluN1a-GluN2C NMDA receptor in intact conformation -
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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | PYD-106-bound Human GluN1a-GluN2C NMDA receptor in intact conformation | |||||||||
![]() | B-factor sharpened map | |||||||||
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Function / homology | ![]() excitatory chemical synaptic transmission / directional locomotion / Synaptic adhesion-like molecules / protein localization to postsynaptic membrane / propylene metabolic process / response to glycine / regulation of monoatomic cation transmembrane transport / glutamate receptor signaling pathway / Assembly and cell surface presentation of NMDA receptors / Neurexins and neuroligins ...excitatory chemical synaptic transmission / directional locomotion / Synaptic adhesion-like molecules / protein localization to postsynaptic membrane / propylene metabolic process / response to glycine / regulation of monoatomic cation transmembrane transport / glutamate receptor signaling pathway / Assembly and cell surface presentation of NMDA receptors / Neurexins and neuroligins / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Chou T-H / Furukawa H | |||||||||
Funding support | ![]()
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![]() | ![]() 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 | ![]() | 226.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18.9 KB 18.9 KB | Display Display | ![]() |
Images | ![]() | 33.3 KB | ||
Others | ![]() ![]() | 20.9 MB 20.9 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8e94MC ![]() 8e92C ![]() 8e93C ![]() 8e96C ![]() 8e97C ![]() 8e98C ![]() 8e99C C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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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_27955_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_27955_half_map_2.map | ||||||||||||
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Annotation | Half map 2 | ||||||||||||
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Density Histograms |
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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-#2 |
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Source (natural) | Organism: ![]() ![]() |
-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: ![]() ![]() |
Molecular weight | Theoretical: 95.081688 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
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 2C
Macromolecule | Name: Glutamate receptor ionotropic, NMDA 2C / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 96.958406 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
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 #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 8 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Macromolecule #7: methyl 4-[(2~{R})-3-ethanoyl-1-[2-(2-methyl-1~{H}-indol-3-yl)ethy...
Macromolecule | Name: methyl 4-[(2~{R})-3-ethanoyl-1-[2-(2-methyl-1~{H}-indol-3-yl)ethyl]-4-oxidanyl-5-oxidanylidene-2~{H}-pyrrol-2-yl]benzoate type: ligand / ID: 7 / Number of copies: 1 / Formula: IWB |
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Molecular weight | Theoretical: 432.468 Da |
Chemical component information | ![]() ChemComp-IWB: |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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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 |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 57.6 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: EMDB MAP EMDB ID: |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.72 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cisTEM (ver. 1.0.2) / Number images used: 60635 |