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- PDB-6irg: Structure of the human GluN1/GluN2A NMDA receptor in the glutamat... -
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Open data
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Basic information
Entry | Database: PDB / ID: 6irg | ||||||||||||||||||
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Title | Structure of the human GluN1/GluN2A NMDA receptor in the glutamate/glycine-bound state at pH 6.3, Class II | ||||||||||||||||||
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Function / homology | ![]() excitatory chemical synaptic transmission / directional locomotion / Synaptic adhesion-like molecules / serotonin metabolic process / protein localization to postsynaptic membrane / propylene metabolic process / response to glycine / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||||||||||||||
Biological species | ![]() ![]() | ||||||||||||||||||
Method | ![]() ![]() ![]() | ||||||||||||||||||
![]() | Zhang, J. / Chang, S. / Zhang, X. / Zhu, S. | ||||||||||||||||||
Funding support | ![]()
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![]() | ![]() 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 |
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Structure visualization
Movie |
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 531.1 KB | Display | ![]() |
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PDB format | ![]() | 443 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 9716MC ![]() 9714C ![]() 9715C ![]() 9717C ![]() 6iraC ![]() 6irfC ![]() 6irhC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | 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.) ![]() ![]() ![]() ![]() #2: Protein | 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.) ![]() ![]() ![]() ![]() |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
Component | Name: 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 | |||||||||||||||||||||||||||||||||||||||||||||
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Molecular weight | Value: 0.38 MDa / Experimental value: NO | |||||||||||||||||||||||||||||||||||||||||||||
Source (natural) | Organism: ![]() ![]() | |||||||||||||||||||||||||||||||||||||||||||||
Source (recombinant) | Organism: ![]() ![]() ![]() | |||||||||||||||||||||||||||||||||||||||||||||
Buffer solution | pH: 6.3 / Details: Solutions were made fresh. | |||||||||||||||||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 3.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() | |||||||||||||||||||||||||||||||||||||||||||||
Specimen support | Details: 15 mA / Grid material: GOLD / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R1.2/1.3 | |||||||||||||||||||||||||||||||||||||||||||||
Vitrification![]() | Instrument: FEI VITROBOT MARK II / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 291 K Details: blot for 2 seconds before plunging in liquid ethane |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source![]() ![]() |
Electron lens | Mode: BRIGHT FIELD![]() |
Image recording | Average 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 scans | Movie frames/image: 40 / Used frames/image: 1-40 |
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Processing
EM software |
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CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 722287 | ||||||||||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 5.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 148840 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT | ||||||||||||||||||||||||||||||||
Atomic model building |
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