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- EMDB-9155: Diheteromeric NMDA receptor GluN1/GluN2A in the '2-Knuckle-Asymme... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-9155 | |||||||||
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Title | Diheteromeric NMDA receptor GluN1/GluN2A in the '2-Knuckle-Asymmetric' conformation, in complex with glycine and glutamate, in the presence of 1 micromolar zinc chloride, and at pH 7.4 | |||||||||
![]() | Diheteromeric NMDA receptor GluN1/GluN2A in the '2-Knuckle-Asymmetric' conformation, in complex with glycine and glutamate, in the presence of 1 micromolar zinc chloride, and at pH 7.4 | |||||||||
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Function / homology | ![]() neurotransmitter receptor transport, plasma membrane to endosome / regulation of response to alcohol / response to ammonium ion / receptor recycling / directional locomotion / response to environmental enrichment / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling ...neurotransmitter receptor transport, plasma membrane to endosome / regulation of response to alcohol / response to ammonium ion / receptor recycling / directional locomotion / response to environmental enrichment / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling / serotonin metabolic process / conditioned place preference / response to hydrogen sulfide / Assembly and cell surface presentation of NMDA receptors / olfactory learning / conditioned taste aversion / dendritic branch / response to other organism / regulation of respiratory gaseous exchange / protein localization to postsynaptic membrane / positive regulation of inhibitory postsynaptic potential / propylene metabolic process / response to glycine / cellular response to magnesium ion / regulation of ARF protein signal transduction / sleep / response to methylmercury / voltage-gated monoatomic cation channel activity / dendritic spine organization / cellular response to dsRNA / response to carbohydrate / regulation of monoatomic cation transmembrane transport / cellular response to lipid / response to morphine / NMDA glutamate receptor activity / locomotion / regulation of NMDA receptor activity / Synaptic adhesion-like molecules / NMDA selective glutamate receptor complex / RAF/MAP kinase cascade / parallel fiber to Purkinje cell synapse / response to manganese ion / calcium ion transmembrane import into cytosol / cellular response to zinc ion / glutamate binding / neuromuscular process / positive regulation of reactive oxygen species biosynthetic process / protein heterotetramerization / regulation of synapse assembly / glycine binding / positive regulation of calcium ion transport into cytosol / regulation of axonogenesis / regulation of dendrite morphogenesis / male mating behavior / dopamine metabolic process / spinal cord development / suckling behavior / action potential / startle response / response to amine / regulation of neuronal synaptic plasticity / monoatomic cation transmembrane transport / modulation of excitatory postsynaptic potential / monoatomic cation transport / response to lithium ion / associative learning / positive regulation of excitatory postsynaptic potential / social behavior / ligand-gated monoatomic ion channel activity / excitatory synapse / cellular response to glycine / positive regulation of dendritic spine maintenance / response to light stimulus / positive regulation of protein targeting to membrane / neuron development / regulation of postsynaptic membrane potential / Unblocking of NMDA receptors, glutamate binding and activation / postsynaptic density, intracellular component / phosphatase binding / cellular response to manganese ion / glutamate receptor binding / multicellular organismal response to stress / long-term memory / prepulse inhibition / monoatomic cation channel activity / calcium ion homeostasis / regulation of neuron apoptotic process / synaptic cleft / glutamate-gated calcium ion channel activity / glutamate-gated receptor activity / presynaptic active zone membrane / response to fungicide / cell adhesion molecule binding / 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 / neurogenesis Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 7.14 Å | |||||||||
![]() | Jalali-Yazdi F / Chowdhury S / Yoshioka C / Gouaux E | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Mechanisms for Zinc and Proton Inhibition of the GluN1/GluN2A NMDA Receptor. Authors: Farzad Jalali-Yazdi / Sandipan Chowdhury / Craig Yoshioka / Eric Gouaux / ![]() Abstract: N-methyl-D-aspartate receptors (NMDARs) play essential roles in memory formation, neuronal plasticity, and brain development, with their dysfunction linked to a range of disorders from ischemia to ...N-methyl-D-aspartate receptors (NMDARs) play essential roles in memory formation, neuronal plasticity, and brain development, with their dysfunction linked to a range of disorders from ischemia to schizophrenia. Zinc and pH are physiological allosteric modulators of NMDARs, with GluN2A-containing receptors inhibited by nanomolar concentrations of divalent zinc and by excursions to low pH. Despite the widespread importance of zinc and proton modulation of NMDARs, the molecular mechanism by which these ions modulate receptor activity has proven elusive. Here, we use cryoelectron microscopy to elucidate the structure of the GluN1/GluN2A NMDAR in a large ensemble of conformations under a range of physiologically relevant zinc and proton concentrations. We show how zinc binding to the amino terminal domain elicits structural changes that are transduced though the ligand-binding domain and result in constriction of the ion channel gate. | |||||||||
History |
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Structure visualization
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 25.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 26.1 KB 26.1 KB | Display Display | ![]() |
Images | ![]() | 148.9 KB | ||
Masks | ![]() | 27 MB | ![]() | |
Others | ![]() ![]() | 11 MB 11 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6mmlMC ![]() 9147C ![]() 9148C ![]() 9149C ![]() 9150C ![]() 9151C ![]() 9152C ![]() 9153C ![]() 9154C ![]() 9156C ![]() 9157C ![]() 9158C ![]() 9159C ![]() 9160C ![]() 9161C ![]() 9162C ![]() 9163C ![]() 9164C ![]() 9165C ![]() 6mm9C ![]() 6mmaC ![]() 6mmbC ![]() 6mmgC ![]() 6mmhC ![]() 6mmiC ![]() 6mmjC ![]() 6mmkC ![]() 6mmmC ![]() 6mmnC ![]() 6mmpC ![]() 6mmrC ![]() 6mmsC ![]() 6mmtC ![]() 6mmuC ![]() 6mmvC ![]() 6mmwC ![]() 6mmxC 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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Annotation | Diheteromeric NMDA receptor GluN1/GluN2A in the '2-Knuckle-Asymmetric' conformation, in complex with glycine and glutamate, in the presence of 1 micromolar zinc chloride, and at pH 7.4 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.71 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
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Density Histograms |
-Half map: Half-maps used for FSC calculations
File | emd_9155_half_map_1.map | ||||||||||||
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Annotation | Half-maps used for FSC calculations | ||||||||||||
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Density Histograms |
-Half map: Half-maps used for FSC calculations
File | emd_9155_half_map_2.map | ||||||||||||
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Annotation | Half-maps used for FSC calculations | ||||||||||||
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Density Histograms |
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Sample components
-Entire : Diheteromeric NMDA receptor GluN1/GluN2A in the '2-Knuckle-Asymme...
Entire | Name: Diheteromeric NMDA receptor GluN1/GluN2A in the '2-Knuckle-Asymmetric' conformation, in complex with glycine and glutamate, in the presence of 1 micromolar zinc chloride, and at pH 7.4 |
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Components |
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-Supramolecule #1: Diheteromeric NMDA receptor GluN1/GluN2A in the '2-Knuckle-Asymme...
Supramolecule | Name: Diheteromeric NMDA receptor GluN1/GluN2A in the '2-Knuckle-Asymmetric' conformation, in complex with glycine and glutamate, in the presence of 1 micromolar zinc chloride, and at pH 7.4 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 Details: Sample was heterologously expressed in TSA-201 cells, detergent solubilized, and affinity purified |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() |
Molecular weight | Theoretical: 500 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: ![]() ![]() |
Molecular weight | Theoretical: 94.189781 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MSTMHLLTFA LLFSCSFARA ACDPKIVNIG AVLSTRKHEQ MFREAVNQAN KRHGSWKIQL NATSVTHKPN AIQMALSVCE DLISSQVYA ILVSHPPTPN DHFTPTPVSY TAGFYRIPVL GLTTRMSIYS DKSIHLSFLR TVPPYSHQSS VWFEMMRVYN W NHIILLVS ...String: MSTMHLLTFA LLFSCSFARA ACDPKIVNIG AVLSTRKHEQ MFREAVNQAN KRHGSWKIQL NATSVTHKPN AIQMALSVCE DLISSQVYA ILVSHPPTPN DHFTPTPVSY TAGFYRIPVL GLTTRMSIYS DKSIHLSFLR TVPPYSHQSS VWFEMMRVYN W NHIILLVS DDHEGRAAQK RLETLLEERE SKAEKVLQFD PGTKNVTALL MEARELEARV IILSASEDDA ATVYRAAAML NM TGSGYVW LVGEREISGN ALRYAPDGII GLQLINGKNE SAHISDAVGV VAQAVHELLE KENITDPPRG CVGNTNIWKT GPL FKRVLM SSKYADGVTG RVEFNEDGDR KFANYSIMNL QNRKLVQVGI YNGTHVIPND RKIIWPGGET EKPRGYQMST RLKI VTIHQ EPFVYVKPTM 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 IFIEIAYK |
-Macromolecule #2: Glutamate receptor ionotropic, NMDA 2A
Macromolecule | Name: Glutamate receptor ionotropic, NMDA 2A / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 93.740352 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MGRLGYWTLL VLPALLVWRD PAQNAAAEKG PPALNIAVLL GHSHDVTERE LRNLWGPEQA TGLPLDVNVV ALLMNRTDPK SLITHVCDL MSGARIHGLV FGDDTDQEAV AQMLDFISSQ TFIPILGIHG GASMIMADKD PTSTFFQFGA SIQQQATVML K IMQDYDWH ...String: MGRLGYWTLL VLPALLVWRD PAQNAAAEKG PPALNIAVLL GHSHDVTERE LRNLWGPEQA TGLPLDVNVV ALLMNRTDPK SLITHVCDL MSGARIHGLV FGDDTDQEAV AQMLDFISSQ TFIPILGIHG GASMIMADKD PTSTFFQFGA SIQQQATVML K IMQDYDWH VFSLVTTIFP GYRDFISFIK TTVDNSFVGW DMQNVITLDT SFEDAKTQVQ LKKIHSSVIL LYCSKDEAVL IL SEARSLG LTGYDFFWIV PSLVSGNTEL IPKEFPSGLI SVSYDDWDYS LEARVRDGLG ILTTAASSML EKFSYIPEAK ASC YGQAEK PETPLHTLHQ FMVNVTWDGK DLSFTEEGYQ VHPRLVVIVL NKDREWEKVG KWENQTLSLR HAVWPRYKSF SDCE PDDNH LSIVTLEEAP FVIVEDIDPL TETCVRNTVP CRKFVKINNS TNEGMNVKKC CKGFCIDILK KLSRTVKFTY DLYLV TNGK HGKKVNNVWN GMIGEVVYQR AVMAVGSLTI NEERSEVVDF SVPFVETGIS VMVSRSNGTV SPSAFLEPFS ASVWVM MFV MLLIVSAIAV FVFEYFSPVG YNRNLAKGKA PHGPSFTIGK AIWLLWGLVF NNSVPVQNPK GTTSKIMVSV WAFFAVI FL ASYTANLAAF MIQEEFVDQV TGLSDKKFQR PHDYSPPFRF GTVPNGSTER NIRNNYPYMH QYMTRFNQRG VEDALVSL K TGKLDAFIYD AAVLNYKAGR DEGCKLVTIG SGYIFATTGY GIALQKGSPW KRQIDLALLQ FVGDGEMEEL ETLWLTGIC HNEKNEVMSS QLDIDNMAGV FYMLAAAMAL SLITFIW |
-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: 30 / 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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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 4.0 mg/mL | |||||||||||||||
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Buffer | pH: 7.4 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: AIR | |||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 291 K / Instrument: FEI VITROBOT MARK IV Details: Sample was blotted for 3 seconds at blot force 1.. | |||||||||||||||
Details | This sample was monodisperse |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 BASE (4k x 4k) / Number grids imaged: 1 / Number real images: 1653 / Average exposure time: 22.0 sec. / Average electron dose: 55.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Initial model |
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Refinement | Protocol: RIGID BODY FIT | ||||||||||
Output model | ![]() PDB-6mml: |