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Yorodumi- EMDB-74385: The LBD-TMD structure of native mouse AMPAR with 3 TARPs 1 CNIH a... -
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Basic information
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| Title | The LBD-TMD structure of native mouse AMPAR with 3 TARPs 1 CNIH and PRRT1/SynDIG4 | |||||||||
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Keywords | iGluR / AMPA receptors / SIGNALING PROTEIN | |||||||||
| Function / homology | Function and homology informationnegative regulation of receptor localization to synapse / negative regulation of anterograde synaptic vesicle transport / Phase 0 - rapid depolarisation / Phase 2 - plateau phase / Cargo concentration in the ER / Activation of AMPA receptors / COPII-mediated vesicle transport / Presynaptic depolarization and calcium channel opening / Synaptic adhesion-like molecules / LGI-ADAM interactions ...negative regulation of receptor localization to synapse / negative regulation of anterograde synaptic vesicle transport / Phase 0 - rapid depolarisation / Phase 2 - plateau phase / Cargo concentration in the ER / Activation of AMPA receptors / COPII-mediated vesicle transport / Presynaptic depolarization and calcium channel opening / Synaptic adhesion-like molecules / LGI-ADAM interactions / Unblocking of NMDA receptors, glutamate binding and activation / Trafficking of GluR2-containing AMPA receptors / cellular response to ammonium ion / axonal spine / positive regulation of locomotion involved in locomotory behavior / Trafficking of AMPA receptors / positive regulation of membrane potential / localization within membrane / response to sucrose / eye blink reflex / positive regulation of protein localization to basolateral plasma membrane / signaling receptor regulator activity / L-type voltage-gated calcium channel complex / regulation of monoatomic ion transmembrane transport / myosin V binding / positive regulation of AMPA receptor activity / cerebellar mossy fiber / neuron spine / postsynaptic neurotransmitter receptor diffusion trapping / proximal dendrite / protein phosphatase 2B binding / response to arsenic-containing substance / regulation of AMPA receptor activity / cellular response to L-glutamate / membrane hyperpolarization / channel regulator activity / protein localization to cell surface / cellular response to dsRNA / long-term synaptic depression / ligand-gated calcium channel activity / nervous system process / dendritic spine membrane / beta-2 adrenergic receptor binding / protein targeting to membrane / voltage-gated calcium channel complex / cellular response to peptide hormone stimulus / cellular response to amine stimulus / response to morphine / response to psychosocial stress / peptide hormone receptor binding / neurotransmitter receptor localization to postsynaptic specialization membrane / perisynaptic space / spinal cord development / neuronal cell body membrane / protein kinase A binding / response to lithium ion / neuromuscular junction development / AMPA glutamate receptor activity / behavioral response to pain / transmission of nerve impulse / regulation of receptor recycling / immunoglobulin binding / adenylate cyclase binding / AMPA glutamate receptor complex / response to electrical stimulus / ionotropic glutamate receptor complex / membrane depolarization / asymmetric synapse / G-protein alpha-subunit binding / glutamate receptor binding / positive regulation of synaptic transmission / conditioned place preference / long-term memory / regulation of postsynaptic membrane neurotransmitter receptor levels / neuronal action potential / voltage-gated calcium channel activity / postsynaptic density, intracellular component / response to fungicide / vesicle-mediated transport / glutamate-gated receptor activity / cellular response to brain-derived neurotrophic factor stimulus / positive regulation of synaptic transmission, glutamatergic / glutamate-gated calcium ion channel activity / somatodendritic compartment / synapse assembly / presynaptic active zone membrane / ionotropic glutamate receptor binding / dendrite membrane / excitatory synapse / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / positive regulation of excitatory postsynaptic potential / hippocampal mossy fiber to CA3 synapse / dendritic shaft / synaptic membrane / response to cocaine / PDZ domain binding / calcium channel regulator activity / neuromuscular junction / synaptic transmission, glutamatergic / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential Similarity search - Function | |||||||||
| Biological species | ![]() | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.75 Å | |||||||||
Authors | Fang CL / Gouaux E | |||||||||
| Funding support | United States, 1 items
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Citation | Journal: Sci Adv / Year: 2026Title: Native AMPA receptor architecture reveals SynDIG4 engagement and auxiliary subunit heterogeneity. Authors: Chengli Fang / Eric Gouaux / ![]() Abstract: AMPA-type glutamate receptors (AMPARs) are complex assemblies whose compositional heterogeneity underlies diverse excitatory signaling in the mammalian brain. Here, we determine high-resolution cryo- ...AMPA-type glutamate receptors (AMPARs) are complex assemblies whose compositional heterogeneity underlies diverse excitatory signaling in the mammalian brain. Here, we determine high-resolution cryo-electron microscopy (cryo-EM) structures of native AMPAR complexes rapidly purified from mouse brain. These structures capture receptors in physiologically relevant assemblies containing distinct combinations of transmembrane AMPA receptor regulatory protein (TARP) and cornichon homolog (CNIH) auxiliary subunits and reveal unambiguous density for the brain-specific protein SynDIG4. The resolved topology and interaction network of SynDIG4 show that it engages the receptor through a CNIH-dependent interface and occupies a position adjacent to structural elements of GluA1 implicated in trafficking and synaptic plasticity. The diversity of auxiliary stoichiometries observed across native complexes highlights a flexible organizational scheme through which AMPARs incorporate distinct regulatory partners. These findings illuminate the organization of native AMPAR assemblies and define the structural context for SynDIG4 function in the mammalian brain. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_74385.map.gz | 217.1 MB | EMDB map data format | |
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| Header (meta data) | emd-74385-v30.xml emd-74385.xml | 26.9 KB 26.9 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_74385_fsc.xml | 13 KB | Display | FSC data file |
| Images | emd_74385.png | 147.7 KB | ||
| Filedesc metadata | emd-74385.cif.gz | 7.3 KB | ||
| Others | emd_74385_additional_1.map.gz emd_74385_half_map_1.map.gz emd_74385_half_map_2.map.gz | 114.1 MB 213.3 MB 213.3 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-74385 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-74385 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9zkuMC ![]() 9zkmC ![]() 9zknC ![]() 9zkoC ![]() 9zkpC ![]() 9zkqC ![]() 9zkrC ![]() 9zksC ![]() 9zktC ![]() 9zkvC ![]() 9zkwC M: atomic model generated by this map C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_74385.map.gz / Format: CCP4 / Size: 229.8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.825 Å | ||||||||||||||||||||||||||||||||||||
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Additional map: #1
| File | emd_74385_additional_1.map | ||||||||||||
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-Half map: #1
| File | emd_74385_half_map_1.map | ||||||||||||
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-Half map: #2
| File | emd_74385_half_map_2.map | ||||||||||||
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Sample components
+Entire : native mouse AMPAR
+Supramolecule #1: native mouse AMPAR
+Macromolecule #1: Glutamate receptor 1
+Macromolecule #2: Glutamate receptor 2
+Macromolecule #3: Protein cornichon homolog 2
+Macromolecule #4: Voltage-dependent calcium channel gamma-2 subunit
+Macromolecule #5: Voltage-dependent calcium channel gamma-8 subunit
+Macromolecule #6: Proline-rich transmembrane protein 1
+Macromolecule #7: PALMITIC ACID
+Macromolecule #8: (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate
+Macromolecule #9: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(tri...
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 8 |
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| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | TFS KRIOS |
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| Image recording | Film or detector model: GATAN K3 BIOCONTINUUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: OTHER / Cs: 2.7 mm / Nominal defocus max: 2.2 µm / Nominal defocus min: 1.2 µm |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Keywords
Authors
United States, 1 items
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Processing
FIELD EMISSION GUN

