+
Open data
-
Basic information
Entry | Database: PDB / ID: 7ldd | ||||||
---|---|---|---|---|---|---|---|
Title | native AMPA receptor | ||||||
![]() |
| ||||||
![]() | ![]() ![]() ![]() ![]() ![]() ![]() | ||||||
Function / homology | ![]() Phase 2 - plateau phase / Activation of AMPA receptors / Phase 0 - rapid depolarisation / negative regulation of receptor localization to synapse / negative regulation of anterograde synaptic vesicle transport / Synaptic adhesion-like molecules / Cargo concentration in the ER / Unblocking of NMDA receptors, glutamate binding and activation / LGI-ADAM interactions / COPII-mediated vesicle transport ...Phase 2 - plateau phase / Activation of AMPA receptors / Phase 0 - rapid depolarisation / negative regulation of receptor localization to synapse / negative regulation of anterograde synaptic vesicle transport / Synaptic adhesion-like molecules / Cargo concentration in the ER / Unblocking of NMDA receptors, glutamate binding and activation / LGI-ADAM interactions / COPII-mediated vesicle transport / Trafficking of AMPA receptors / cellular response to amine stimulus / axonal spine / Trafficking of GluR2-containing AMPA receptors / positive regulation of membrane potential / localization within membrane / cellular response to ammonium ion / neurotransmitter receptor transport, postsynaptic endosome to lysosome / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Yu, J. / Rao, P. / Gouaux, E. | ||||||
Funding support | ![]()
| ||||||
![]() | ![]() Title: Hippocampal AMPA receptor assemblies and mechanism of allosteric inhibition. Authors: Jie Yu / Prashant Rao / Sarah Clark / Jaba Mitra / Taekjip Ha / Eric Gouaux / ![]() Abstract: AMPA-selective glutamate receptors mediate the transduction of signals between the neuronal circuits of the hippocampus. The trafficking, localization, kinetics and pharmacology of AMPA receptors are ...AMPA-selective glutamate receptors mediate the transduction of signals between the neuronal circuits of the hippocampus. The trafficking, localization, kinetics and pharmacology of AMPA receptors are tuned by an ensemble of auxiliary protein subunits, which are integral membrane proteins that associate with the receptor to yield bona fide receptor signalling complexes. Thus far, extensive studies of recombinant AMPA receptor-auxiliary subunit complexes using engineered protein constructs have not been able to faithfully elucidate the molecular architecture of hippocampal AMPA receptor complexes. Here we obtain mouse hippocampal, calcium-impermeable AMPA receptor complexes using immunoaffinity purification and use single-molecule fluorescence and cryo-electron microscopy experiments to elucidate three major AMPA receptor-auxiliary subunit complexes. The GluA1-GluA2, GluA1-GluA2-GluA3 and GluA2-GluA3 receptors are the predominant assemblies, with the auxiliary subunits TARP-γ8 and CNIH2-SynDIG4 non-stochastically positioned at the B'/D' and A'/C' positions, respectively. We further demonstrate how the receptor-TARP-γ8 stoichiometry explains the mechanism of and submaximal inhibition by a clinically relevant, brain-region-specific allosteric inhibitor. #1: ![]() Title: Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM. Authors: Yan Zhao / Shanshuang Chen / Adam C Swensen / Wei-Jun Qian / Eric Gouaux / ![]() Abstract: Glutamate-gated AMPA receptors mediate the fast component of excitatory signal transduction at chemical synapses throughout all regions of the mammalian brain. AMPA receptors are tetrameric ...Glutamate-gated AMPA receptors mediate the fast component of excitatory signal transduction at chemical synapses throughout all regions of the mammalian brain. AMPA receptors are tetrameric assemblies composed of four subunits, GluA1-GluA4. Despite decades of study, the subunit composition, subunit arrangement, and molecular structure of native AMPA receptors remain unknown. Here we elucidate the structures of 10 distinct native AMPA receptor complexes by single-particle cryo-electron microscopy (cryo-EM). We find that receptor subunits are arranged nonstochastically, with the GluA2 subunit preferentially occupying the B and D positions of the tetramer and with triheteromeric assemblies comprising a major population of native AMPA receptors. Cryo-EM maps define the structure for S2-M4 linkers between the ligand-binding and transmembrane domains, suggesting how neurotransmitter binding is coupled to ion channel gating. | ||||||
History |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | Molecule: ![]() ![]() |
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 830.5 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 658.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
---|
-Related structure data
Related structure data | ![]() 23283MC ![]() 7ldeC ![]() 7lepC M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
-Protein , 4 types, 8 molecules ACBDEFGH
#1: Protein | ![]() Mass: 101678.969 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() #2: Protein | ![]() Mass: 98899.883 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() #3: Protein | Mass: 18948.420 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() #4: Protein | Mass: 43502.938 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() |
---|
-Antibody , 3 types, 6 molecules ILJMKN
#5: Antibody | Mass: 27511.527 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() ![]() #6: Antibody | Mass: 25111.660 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() Production host: ![]() #7: Antibody | Mass: 27975.439 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() Production host: ![]() |
---|
-Sugars , 2 types, 12 molecules ![](data/chem/img/NAG.gif)
#8: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose ![]() #14: Sugar | ChemComp-NAG / ![]() |
---|
-Non-polymers , 9 types, 40 molecules ![](data/chem/img/ZK1.gif)
![](data/chem/img/R16.gif)
![](data/chem/img/OCT.gif)
![](data/chem/img/HP6.gif)
![](data/chem/img/D10.gif)
![](data/chem/img/D12.gif)
![](data/chem/img/C14.gif)
![](data/chem/img/DD9.gif)
![](data/chem/img/XVD.gif)
![](data/chem/img/R16.gif)
![](data/chem/img/OCT.gif)
![](data/chem/img/HP6.gif)
![](data/chem/img/D10.gif)
![](data/chem/img/D12.gif)
![](data/chem/img/C14.gif)
![](data/chem/img/DD9.gif)
![](data/chem/img/XVD.gif)
#9: Chemical | ChemComp-ZK1 / {[ ![]() #10: Chemical | ![]() #11: Chemical | ChemComp-OCT / ![]() #12: Chemical | ChemComp-HP6 / ![]() #13: Chemical | ChemComp-D10 / ![]() #15: Chemical | ChemComp-D12 / ![]() #16: Chemical | ChemComp-C14 / ![]() #17: Chemical | ChemComp-DD9 / ![]() #18: Chemical | |
---|
-Details
Has ligand of interest | Y |
---|
-Experimental details
-Experiment
Experiment | Method: ![]() |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
-
Sample preparation
Component |
| ||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Source (natural) |
| ||||||||||||||||||||||||||||||
Source (recombinant) |
| ||||||||||||||||||||||||||||||
Buffer solution | pH: 8 | ||||||||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() | ||||||||||||||||||||||||||||||
Vitrification![]() | Cryogen name: ETHANE |
-
Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source![]() ![]() |
Electron lens | Mode: BRIGHT FIELD![]() |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-
Processing
CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
---|---|
3D reconstruction![]() | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 829000 / Symmetry type: POINT |