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- EMDB-8097: Cryo-EM structure of GluN1/GluN2B NMDA receptor in the glutamate/... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-8097 | |||||||||
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Title | Cryo-EM structure of GluN1/GluN2B NMDA receptor in the glutamate/glycine-bound conformation | |||||||||
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![]() | ligand-gated ion channel / synaptic transmission / SIGNALING PROTEIN | |||||||||
Function / homology | ![]() NMDA glutamate receptor activity / NMDA selective glutamate receptor complex / response to zinc ion / response to magnesium ion / regulation of membrane potential / excitatory postsynaptic potential / long-term synaptic potentiation / late endosome / chemical synaptic transmission / postsynaptic membrane ...NMDA glutamate receptor activity / NMDA selective glutamate receptor complex / response to zinc ion / response to magnesium ion / regulation of membrane potential / excitatory postsynaptic potential / long-term synaptic potentiation / late endosome / chemical synaptic transmission / postsynaptic membrane / lysosome / neuron projection / metal ion binding / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 7.0 Å | |||||||||
![]() | Zhu S / Stein AR | |||||||||
![]() | ![]() Title: Mechanism of NMDA Receptor Inhibition and Activation. Authors: Shujia Zhu / Richard A Stein / Craig Yoshioka / Chia-Hsueh Lee / April Goehring / Hassane S Mchaourab / Eric Gouaux / ![]() Abstract: N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated, calcium-permeable ion channels that mediate synaptic transmission and underpin learning and memory. NMDAR dysfunction is directly ...N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated, calcium-permeable ion channels that mediate synaptic transmission and underpin learning and memory. NMDAR dysfunction is directly implicated in diseases ranging from seizure to ischemia. Despite its fundamental importance, little is known about how the NMDAR transitions between inactive and active states and how small molecules inhibit or activate ion channel gating. Here, we report electron cryo-microscopy structures of the GluN1-GluN2B NMDA receptor in an ensemble of competitive antagonist-bound states, an agonist-bound form, and a state bound with agonists and the allosteric inhibitor Ro25-6981. Together with double electron-electron resonance experiments, we show how competitive antagonists rupture the ligand binding domain (LBD) gating "ring," how agonists retain the ring in a dimer-of-dimers configuration, and how allosteric inhibitors, acting within the amino terminal domain, further stabilize the LBD layer. These studies illuminate how the LBD gating ring is fundamental to signal transduction and gating in NMDARs. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 29.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.3 KB 14.3 KB | Display Display | ![]() |
Images | ![]() | 160.2 KB | ||
Filedesc metadata | ![]() | 6.6 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 504.7 KB | Display | ![]() |
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Full document | ![]() | 504.2 KB | Display | |
Data in XML | ![]() | 4.3 KB | Display | |
Data in CIF | ![]() | 4.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 5iouMC ![]() 8098C ![]() 8101C ![]() 8102C ![]() 8103C ![]() 8104C ![]() 8105C ![]() 8106C ![]() 5iovC ![]() 5ipqC ![]() 5iprC ![]() 5ipsC ![]() 5iptC ![]() 5ipuC ![]() 5ipvC C: citing same article ( M: atomic model generated by this map |
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Similar structure data |
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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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Voxel size | X=Y=Z: 1.07 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : GluN1-GluN2B NMDA receptor
Entire | Name: GluN1-GluN2B NMDA receptor |
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Components |
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-Supramolecule #1: GluN1-GluN2B NMDA receptor
Supramolecule | Name: GluN1-GluN2B NMDA receptor / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: N-methyl-D-aspartate receptor subunit NR1-8a
Macromolecule | Name: N-methyl-D-aspartate receptor subunit NR1-8a / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 92.651234 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: DPKIVNIGAV LSTKKHEQIF REAVNQANFF HFTRKIQLNA TSVTHRPNAI QMALSVCEDL ISSQVYAILV SHPPAPTDHL TPTPISYTA GFYRIPVIGL TTRMSIYSDK SIHLSFLRTV PPYSHQALVW FEMMRLFNWN HVILIVSDDH EGRAAQKKLE T LLEEKESK ...String: DPKIVNIGAV LSTKKHEQIF REAVNQANFF HFTRKIQLNA TSVTHRPNAI QMALSVCEDL ISSQVYAILV SHPPAPTDHL TPTPISYTA GFYRIPVIGL TTRMSIYSDK SIHLSFLRTV PPYSHQALVW FEMMRLFNWN HVILIVSDDH EGRAAQKKLE T LLEEKESK ADKVLQFEPG TKNLTALLLE AKELEARVII LSASEDDATA VYKSAAMLDM TGAGYVWLVG EREISGSALR YA PDGIIGL QLINGKNESA HISDAVAVVA QAIHELFEME QITDPPRGCV GNTNIWKTGP LFKRVLMSSK YPDGVTGRIE FNE DGDRKF AQYSIMNLQN RKLVQVGIFD GSYIIQNDRK IIWPGGETER PQGYQMSTRL KIVTIHQEPF VYVRPTTSDG TCRE EYTIN GDPIKKVICN GPDETIPGRP TVPQCCYGFC VDLLIKLARE MDFTYEVHLV ADGKFGTQER VNNSNAAAWN GMMGE LLSG QADMIVAPLT INNERAQYIE FSKPFKYQGL TILVKKEIPR STLDSFMQPF QSTLWLLVGL SVHVVAVMLY LLDRFS PFG RFEDALTLSS AMWFSWRVLL NSGLGEGAPR SFSARILGMV WAGFAMIIVA SYTANLAAFL VLRRPEERIT GINDPRL RN PSDKFIYATV KQSSVDIYFR RQVELSTMYR HMEKHNYESA AEAIQAVRDN KLHAFIWDSA VLEFEASQKC DLVTTGEL F FRSGFGIGMR KDSPWKQEVS LNILKSHENG FMEELDKTWV RYQECDSRSN APATLTFENM AGVFMLVAGG IVAGIFLIF IEIAYKSRAE AKRMKGLEVL FQ UniProtKB: Glutamate receptor ionotropic, NMDA 1 |
-Macromolecule #2: Ionotropic glutamate receptor subunit NR2B
Macromolecule | Name: Ionotropic glutamate receptor subunit NR2B / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 93.234742 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MRPTEACCYL KISLIILFYS RAYAQKHPNM DIAVILVGTT EEVAIKDVHE KDDFHHLPVT PRVELVTMQE SDPKSIITRI CDLMSDKKV QGVVFGDDTD QEAIAQILDF ISVQTLTPIL GIHGGSSMIM ADKEEASMFF QFGPSIEQQA SVMLNIMEEY D WYIFSIVT ...String: MRPTEACCYL KISLIILFYS RAYAQKHPNM DIAVILVGTT EEVAIKDVHE KDDFHHLPVT PRVELVTMQE SDPKSIITRI CDLMSDKKV QGVVFGDDTD QEAIAQILDF ISVQTLTPIL GIHGGSSMIM ADKEEASMFF QFGPSIEQQA SVMLNIMEEY D WYIFSIVT TYFPGYQDFE NKVRSTIENS FVGWELEEVI HLDMSLDDID SKIQNQLKKL QSPVILLYCT KEEATYIFEV AH SVGLTGY GFTWIVPSLV AGDTDTVPDE FPTGLISVSY DEWDYDLPAR VRDGIAIITT AASTMLSEHN SIPQSKSSCN NIQ ESRVYE AHMLKRYLIN VTFEGRDLSF SEDGYQMHPK LVIILLNQER KWERVGKYKD RSLKMWPVFD LYPNSEEHKD EHLS IVTLE EAPFVIVEDV DPLSGTCMRN TVPCRKQIRP ENRTEEGGNY IKRCCKGFCI DILKKIAKTV KFTYDLYLVT NGKHG KKIN GVWNGMIGEV VTKRAYMAVG SLTINEERSE VVDFSVPFIE TGISVMVSRS NGTVSPSAFL EPFSADVWVM MFVMLL IVS AVAVFVFEYF SPVGYNGPSF TIGKAIWLLW GLVFNNSLPV QNPKGTTSKI MVSVWAFFAV IFLASYTANL AAFMIQR RY VDQVSGLSDK KFQRPNDFSP AFRFGTVPNG STERNIRNNY LEMHSYMVKF NQRSVQDALL SLKSGKLDAF IYDAAVLN Y MAGRDEGCKL VTIGSGKVFA TTGYGIAIQK DSGWKRQVDL AILQLFGDGE MEELEALWLT GICHNEKNEV MSSQLDIDN MAGVFYMLAA AMALSLITFI MEHLF UniProtKB: Glutamate receptor ionotropic, NMDA 2B |
-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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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 6.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average exposure time: 8.0 sec. / Average electron dose: 8.7 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Cs: 2.0 mm / Nominal defocus max: 4.0 µm / Nominal defocus min: 2.5 µm |
Sample stage | Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |