|Entry||Database: PDB / ID: 6mma|
|Title||Diheteromeric NMDA receptor GluN1/GluN2A in the 'Extended' conformation, in complex with glycine and glutamate, in the presence of 1 micromolar zinc chloride, and at pH 6.1|
|Keywords||TRANSPORT PROTEIN / Ligand-gated Ion Channel / NMDA Receptor / ionotropic Glutamate Receptors / membrane protein|
|Function / homology||EPHB-mediated forward signaling / Receptor family ligand binding region / Receptor, ligand binding region / Glutamate [NMDA] receptor, epsilon subunit, C-terminal / Ionotropic glutamate receptor, metazoa / Ionotropic glutamate receptor / Ligand-gated ion channel / Calmodulin-binding domain C0, NMDA receptor, NR1 subunit / Unblocking of NMDA receptors, glutamate binding and activation / Periplasmic binding protein-like I ...EPHB-mediated forward signaling / Receptor family ligand binding region / Receptor, ligand binding region / Glutamate [NMDA] receptor, epsilon subunit, C-terminal / Ionotropic glutamate receptor, metazoa / Ionotropic glutamate receptor / Ligand-gated ion channel / Calmodulin-binding domain C0, NMDA receptor, NR1 subunit / Unblocking of NMDA receptors, glutamate binding and activation / Periplasmic binding protein-like I / N-methyl D-aspartate receptor 2B3 C-terminus / CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde / rt:r-rno-442982: / RAF/MAP kinase cascade / Synaptic adhesion-like molecules / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Calmodulin-binding domain C0 of NMDA receptor NR1 subunit / Ligated ion channel L-glutamate- and glycine-binding site / response to ammonium ion / dendritic branch / positive regulation of Schwann cell migration / response to other organism / cellular response to lipid / ligand-gated ion channel activity involved in regulation of presynaptic membrane potential / glutamate-gated calcium ion channel activity / cellular response to dsRNA / neurotransmitter binding / calcium ion transmembrane import into cytosol / action potential / glutamate receptor binding / voltage-gated cation channel activity / cellular response to zinc ion / glycine binding / parallel fiber to Purkinje cell synapse / response to carbohydrate / cellular response to magnesium ion / NMDA glutamate receptor activity / glutamate binding / NMDA selective glutamate receptor complex / synaptic membrane / dendrite membrane / response to methylmercury / positive regulation of cysteine-type endopeptidase activity / positive regulation of reactive oxygen species biosynthetic process / response to manganese ion / spinal cord development / postsynaptic density membrane / response to amine / positive regulation of calcium ion transport into cytosol / response to light stimulus / excitatory synapse / excitatory postsynaptic potential / positive regulation of dendritic spine maintenance / synaptic cleft / positive regulation of excitatory postsynaptic potential / phosphatase binding / response to cocaine / response to fungicide / integral component of postsynaptic density membrane / cerebral cortex development / transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential / ionotropic glutamate receptor activity / cellular response to growth factor stimulus / long-term synaptic potentiation / ionotropic glutamate receptor signaling pathway / cellular response to amino acid stimulus / cell adhesion molecule binding / hippocampus development / cellular response to manganese ion / positive regulation of cell death / hippocampal mossy fiber to CA3 synapse / memory / integral component of presynaptic membrane / regulation of long-term neuronal synaptic plasticity / presynaptic membrane / terminal bouton / rhythmic process / response to calcium ion / response to organic cyclic compound / protein heterotetramerization / learning or memory / protein tetramerization / chemical synaptic transmission / scaffold protein binding / amyloid-beta binding / ATPase binding / response to ethanol / dendritic spine / postsynaptic density / protein dimerization activity / protein-containing complex binding / cell junction / synapse / neuron projection / response to drug / glutamatergic synapse / neuronal cell body / signaling receptor binding / protein heterodimerization activity / protein kinase binding|
Function and homology information
|Specimen source||Rattus norvegicus (Norway rat)|
|Method||ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / 6.31 Å resolution|
|Authors||Jalali-Yazdi, F. / Chowdhury, S. / Yoshioka, C. / Gouaux, E.|
|Citation||Journal: Cell / Year: 2018|
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.
SummaryFull reportAbout validation report
|Date||Deposition: Sep 29, 2018 / Release: Nov 28, 2018|
|Structure viewer||Molecule: |
Downloads & links
A: Glutamate receptor ionotropic, NMDA 1
B: Glutamate receptor ionotropic, NMDA 2A
C: Glutamate receptor ionotropic, NMDA 1
D: Glutamate receptor ionotropic, NMDA 2A
Mass: 94189.781 Da / Num. of mol.: 2 / Fragment: UNP residues 1-838 / Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Grin1, Nmdar1 / Variant: 1a / Cell line (production host): TSA-201 / Organ (production host): Kidney / Production host: Homo sapiens (human) / References: UniProt: P35439
Mass: 93740.352 Da / Num. of mol.: 2 / Fragment: UNP residues 1-837 / Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Grin2a / Cell line (production host): TSA-201 / Organ (production host): Kidney / Production host: Homo sapiens (human) / References: UniProt: Q00959
|Experiment||Method: ELECTRON MICROSCOPY|
|EM experiment||Aggregation state: PARTICLE / Reconstruction method: single particle reconstruction|
|Component||Name: Diheteromeric NMDA receptor GluN1/GluN2A in the 'Extended' conformation, in complex with glycine and glutamate, in the presence of 1 micromolar zinc chloride, and at pH 6.1|
Details: Sample was heterologously expressed in TSA-201 cells, detergent solubilized, and affinity purified
Entity ID: 1,
|Molecular weight||Value: 0.5 MDa / Experimental value: NO||Source (natural)||Organism: Rattus norvegicus (Norway rat)||Source (recombinant)||Cell: TSA-201 / Organism: Homo sapiens (human)||Buffer solution||pH: 6.1||Buffer component|
|Specimen||Conc.: 4 / Details: This sample was monodisperse / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES||Specimen support||Grid material: GOLD / Grid mesh size: 300 / Grid type: Quantifoil R1.2/1.3||Vitrification||Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 291 / Details: sample was blotted for 3 seconds at blot force 1.|
-Electron microscopy imaging
Model: Titan Krios / Image courtesy: FEI Company
|Microscopy||Microscope model: FEI TITAN KRIOS|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 / Illumination mode: FLOOD BEAM|
|Electron lens||Mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7|
|Image recording||Average exposure time: 22 / Electron dose: 52 / Film or detector model: GATAN K2 BASE (4k x 4k) / Number of grids imaged: 1 / Number of real images: 2163|
|Software||Name: PHENIX / Version: 1.13_2998: / Classification: refinement|
|CTF correction||Type: PHASE FLIPPING AND AMPLITUDE CORRECTION|
|Symmetry||Point symmetry: C1|
|3D reconstruction||Resolution: 6.31 / Resolution method: FSC 0.143 CUT-OFF / Number of particles: 86310 / Algorithm: FOURIER SPACE / Symmetry type: POINT|
|Atomic model building||Ref protocol: RIGID BODY FIT|
|Atomic model building|
-Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)
EMDB accession codes are about to change! (news from PDBe EMDB page)
- The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force. (see PDBe EMDB page)
- The EM Navigator/Yorodumi systems omit the EMD- prefix.
Related info.: Q: What is "EMD"? / ID/Accession-code notation in Yorodumi/EM Navigator
-Jul 12, 2017. Major update of PDB
Major update of PDB
- wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary. This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated. See below links for details.
- In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software). Now, EM Navigator and Yorodumi are based on the updated data.
+Jun 16, 2017. Omokage search with filter
Omokage search with filter
- Result of Omokage search can be filtered by keywords and the database types
Related info.: Omokage search
+Sep 15, 2016. EM Navigator & Yorodumi renewed
EM Navigator & Yorodumi renewed
- New versions of EM Navigator and Yorodumi started
Related info.: Changes in new EM Navigator and Yorodumi
+Aug 31, 2016. New EM Navigator & Yorodumi
New EM Navigator & Yorodumi
- In 15th Sep 2016, the development versions of EM Navigator and Yorodumi will replace the official versions.
- Current version will continue as 'legacy version' for some time.
Related info.: Changes in new EM Navigator and Yorodumi / EM Navigator / Yorodumi
Thousand views of thousand structures
- Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
- This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
Related info.: EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi