[English] 日本語
Yorodumi
- PDB-6irg: Structure of the human GluN1/GluN2A NMDA receptor in the glutamat... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6irg
TitleStructure of the human GluN1/GluN2A NMDA receptor in the glutamate/glycine-bound state at pH 6.3, Class II
Components
  • Glutamate receptor ionotropic, NMDA 1
  • Glutamate receptor ionotropic, NMDA 2A
KeywordsMEMBRANE PROTEIN / ionotropic glutamate receptors / NMDA receptors / synaptic protein
Function / homology
Function and homology information


neurotransmitter receptor complex / excitatory chemical synaptic transmission / directional locomotion / serotonin metabolic process / Synaptic adhesion-like molecules / protein localization to postsynaptic membrane / response to glycine / propylene metabolic process / sleep / regulation of monoatomic cation transmembrane transport ...neurotransmitter receptor complex / excitatory chemical synaptic transmission / directional locomotion / serotonin metabolic process / Synaptic adhesion-like molecules / protein localization to postsynaptic membrane / response to glycine / propylene metabolic process / sleep / regulation of monoatomic cation transmembrane transport / Assembly and cell surface presentation of NMDA receptors / NMDA glutamate receptor activity / Neurexins and neuroligins / transmitter-gated monoatomic ion channel activity / NMDA selective glutamate receptor complex / ligand-gated sodium channel activity / glutamate receptor signaling pathway / calcium ion transmembrane import into cytosol / glutamate binding / protein heterotetramerization / glycine binding / positive regulation of reactive oxygen species biosynthetic process / positive regulation of calcium ion transport into cytosol / startle response / Negative regulation of NMDA receptor-mediated neuronal transmission / dopamine metabolic process / monoatomic ion channel complex / Unblocking of NMDA receptors, glutamate binding and activation / monoatomic cation transmembrane transport / regulation of neuronal synaptic plasticity / monoatomic cation transport / Long-term potentiation / positive regulation of excitatory postsynaptic potential / excitatory synapse / ligand-gated monoatomic ion channel activity / synaptic cleft / calcium ion homeostasis / MECP2 regulates neuronal receptors and channels / glutamate-gated calcium ion channel activity / sensory perception of pain / EPHB-mediated forward signaling / cytoplasmic vesicle membrane / response to amphetamine / sodium ion transmembrane transport / ionotropic glutamate receptor signaling pathway / Ras activation upon Ca2+ influx through NMDA receptor / positive regulation of synaptic transmission, glutamatergic / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / regulation of membrane potential / excitatory postsynaptic potential / synaptic transmission, glutamatergic / neurogenesis / long-term synaptic potentiation / synaptic membrane / protein catabolic process / postsynaptic density membrane / visual learning / terminal bouton / brain development / negative regulation of protein catabolic process / regulation of synaptic plasticity / response to wounding / calcium ion transmembrane transport / memory / synaptic vesicle / signaling receptor activity / amyloid-beta binding / presynaptic membrane / RAF/MAP kinase cascade / chemical synaptic transmission / response to ethanol / postsynaptic membrane / dendritic spine / learning or memory / calmodulin binding / postsynaptic density / neuron projection / positive regulation of apoptotic process / response to xenobiotic stimulus / dendrite / calcium ion binding / synapse / endoplasmic reticulum membrane / protein-containing complex binding / glutamatergic synapse / cell surface / positive regulation of transcription by RNA polymerase II / zinc ion binding / plasma membrane / cytoplasm
Similarity search - Function
Glutamate [NMDA] receptor, epsilon subunit, C-terminal / N-methyl D-aspartate receptor 2B3 C-terminus / : / : / Ionotropic glutamate receptor, metazoa / Ligated ion channel L-glutamate- and glycine-binding site / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Ligated ion channel L-glutamate- and glycine-binding site / Ligand-gated ion channel / : ...Glutamate [NMDA] receptor, epsilon subunit, C-terminal / N-methyl D-aspartate receptor 2B3 C-terminus / : / : / Ionotropic glutamate receptor, metazoa / Ligated ion channel L-glutamate- and glycine-binding site / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Ligated ion channel L-glutamate- and glycine-binding site / Ligand-gated ion channel / : / Ionotropic glutamate receptor / Eukaryotic homologues of bacterial periplasmic substrate binding proteins. / Receptor, ligand binding region / Receptor family ligand binding region / Periplasmic binding protein-like I
Similarity search - Domain/homology
Glutamate receptor ionotropic, NMDA 1 / Glutamate receptor ionotropic, NMDA 2A
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 5.5 Å
AuthorsZhang, J. / Chang, S. / Zhang, X. / Zhu, S.
Funding support China, 5items
OrganizationGrant numberCountry
National Basic Research Program of China (973 Program)2017YFA0504803 China
National Basic Research Program of China (973 Program)2018YFA0507700 China
National Basic Research Program of China (973 Program)2017YFA0505700 China
National Natural Science Foundation of China31771115 China
Chinese Academy of SciencesXDBS32020000 China
CitationJournal: Cell Rep / Year: 2018
Title: Structural Basis of the Proton Sensitivity of Human GluN1-GluN2A NMDA Receptors.
Authors: Jin-Bao Zhang / Shenghai Chang / Pan Xu / Miao Miao / Hangjun Wu / Youyi Zhang / Tongtong Zhang / Han Wang / Jilin Zhang / Chun Xie / Nan Song / Cheng Luo / Xing Zhang / Shujia Zhu /
Abstract: N-methyl-D-aspartate (NMDA) receptors are critical for synaptic development and plasticity. While glutamate is the primary agonist, protons can modulate NMDA receptor activity at synapses during ...N-methyl-D-aspartate (NMDA) receptors are critical for synaptic development and plasticity. While glutamate is the primary agonist, protons can modulate NMDA receptor activity at synapses during vesicle exocytosis by mechanisms that are unknown. We used cryo-electron microscopy to solve the structures of the human GluN1-GluN2A NMDA receptor at pH 7.8 and pH 6.3. Our structures demonstrate that the proton sensor predominantly resides in the N-terminal domain (NTD) of the GluN2A subunit and reveal the allosteric coupling mechanism between the proton sensor and the channel gate. Under high-pH conditions, the GluN2A-NTD adopts an "open-and-twisted" conformation. However, upon protonation at the lower pH, the GluN2A-NTD transits from an open- to closed-cleft conformation, causing rearrangements between the tetrameric NTDs and agonist-binding domains. The conformational mobility observed in our structures (presumably from protonation) is supported by molecular dynamics simulation. Our findings reveal the structural mechanisms by which protons allosterically inhibit human GluN1-GluN2A receptor activity.
History
DepositionNov 12, 2018Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jan 16, 2019Provider: repository / Type: Initial release
Revision 1.1Jun 5, 2019Group: Advisory / Data collection ...Advisory / Data collection / Derived calculations / Refinement description
Category: em_3d_fitting_list / pdbx_validate_close_contact ...em_3d_fitting_list / pdbx_validate_close_contact / struct_conn / struct_conn_type
Revision 1.2Oct 23, 2024Group: Author supporting evidence / Data collection ...Author supporting evidence / Data collection / Database references / Refinement description / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / em_3d_fitting_list / em_admin / pdbx_audit_support / pdbx_entry_details / pdbx_initial_refinement_model / pdbx_modification_feature
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _em_3d_fitting_list.accession_code / _em_3d_fitting_list.initial_refinement_model_id / _em_3d_fitting_list.source_name / _em_3d_fitting_list.type / _em_admin.last_update / _pdbx_audit_support.funding_organization

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-9716
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
C: Glutamate receptor ionotropic, NMDA 1
A: Glutamate receptor ionotropic, NMDA 1
B: Glutamate receptor ionotropic, NMDA 2A
D: Glutamate receptor ionotropic, NMDA 2A


Theoretical massNumber of molelcules
Total (without water)379,0574
Polymers379,0574
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: cross-linking
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area21800 Å2
ΔGint-165 kcal/mol
Surface area153000 Å2

-
Components

#1: Protein Glutamate receptor ionotropic, NMDA 1 / N-methyl-D-aspartate receptor subunit NR1 / NMD-R1


Mass: 95336.219 Da / Num. of mol.: 2 / Mutation: G612R
Source method: isolated from a genetically manipulated source
Details: 2 mM Glycine / Source: (gene. exp.) Homo sapiens (human) / Gene: Grin1, NMDAR1 / Cell line (production host): HEK293S GnTl- / Production host: Homo sapiens (human) / References: UniProt: Q05586
#2: Protein Glutamate receptor ionotropic, NMDA 2A / N-methyl D-aspartate receptor subtype 2A / hNR2A


Mass: 94192.172 Da / Num. of mol.: 2 / Mutation: E656R, E657R
Source method: isolated from a genetically manipulated source
Details: 2 mM L-Glutamate / Source: (gene. exp.) Homo sapiens (human) / Gene: Grin2a / Cell line (production host): HEK293S GnTl- / Production host: Homo sapiens (human) / References: UniProt: Q12879
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: Human GluN1/GluN2A NMDA receptors in the glutamate/glycine bound state at pH 6.3, Class II
Type: COMPLEX / Details: with the presence of Glycine,L-glutamate and EDTA / Entity ID: all / Source: RECOMBINANT
Molecular weightValue: 0.38 MDa / Experimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human) / Cell: HEK293S GnTl- / Plasmid: pEG-Bacmam
Buffer solutionpH: 6.3 / Details: Solutions were made fresh.
Buffer component
IDConc.NameFormulaBuffer-ID
1150 mMsodium chlorideNaCl1
220 mMMESC6H13NO4S1
30.05 mMEDTA(HO2CCH2)2NCH2CH2N(CH2CO2H)21
40.005 mMCholesteryl Hemisuccinate Tris SaltC31H50O4(C4H11NO3)1
50.001 g/mLDigitoninC56H92O291
60.1 mMCHAPSOC32H58N2O8S1
72 mMGlycineNH2CH2COOH1
82 mML-Glutamic acid monosodium salt hydrateC5H8NNaO4(xH2O)1
SpecimenConc.: 3.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: Tetrameric GluN1/GluN2A NMDA receptors
Specimen supportDetails: 15 mA / Grid material: GOLD / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK II / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 291 K
Details: blot for 2 seconds before plunging in liquid ethane

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD
Image recordingAverage exposure time: 12 sec. / Electron dose: 56 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 4
Image scansMovie frames/image: 40 / Used frames/image: 1-40

-
Processing

EM software
IDNameCategory
1Gautomatchparticle selection
4GctfCTF correction
7UCSF Chimeramodel fitting
13PHENIXmodel refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 722287
3D reconstructionResolution: 5.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 148840 / Symmetry type: POINT
Atomic model buildingProtocol: RIGID BODY FIT
Atomic model building

3D fitting-ID: 1 / Source name: PDB / Type: experimental model

IDPDB-IDPdb chain-IDAccession codeInitial refinement model-ID
14PE5

4pe5

A4PE51
25TQ0

5tq0

B5TQ02
35H8F

5h8f

A5H8F3
44PE5

4pe5

B4PE51
54PE5

4pe5

C4PE51
64PE5

4pe5

D4PE51
75H8F

5h8f

B5H8F3

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
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.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
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.
  • 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.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
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.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

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

Read more