9NR9
The structure of GluA1/A4 LBD-TMD with 2 TARPs
Summary for 9NR9
| Entry DOI | 10.2210/pdb9nr9/pdb |
| EMDB information | 49726 |
| Descriptor | Voltage-dependent calcium channel gamma-2 subunit, Glutamate receptor 1, Isoform 2 of Glutamate receptor 4, ... (4 entities in total) |
| Functional Keywords | iglur, cp-ampa receptors, membrane protein |
| Biological source | Rattus norvegicus (Norway rat) More |
| Total number of polymer chains | 6 |
| Total formula weight | 236923.37 |
| Authors | Fang, C.L.,Gouaux, E. (deposition date: 2025-03-14, release date: 2025-07-02, Last modification date: 2025-11-26) |
| Primary citation | Fang, C.L.,Spangler, C.J.,Park, J.,Sheldon, N.,Trussell, L.O.,Gouaux, E. Gating and noelin clustering of native Ca 2+ -permeable AMPA receptors. Nature, 645:526-534, 2025 Cited by PubMed Abstract: AMPA-type ionotropic glutamate receptors (AMPARs) are integral to fast excitatory synaptic transmission and have vital roles in synaptic plasticity, motor coordination, learning and memory. Whereas extensive structural studies have been conducted on recombinant AMPARs and native calcium-impermeable (CI)-AMPARs alongside their auxiliary proteins, the molecular architecture of native calcium-permeable (CP)-AMPARs has remained undefined. Here, to determine the subunit composition, physiological architecture and gating mechanisms of CP-AMPARs, we visualize these receptors, immunoaffinity purified from rat cerebella, and resolve their structures using cryo-electron microscopy (cryo-EM). Our results indicate that the predominant assembly consists of GluA1 and GluA4 subunits, with the GluA4 subunit occupying the B and D positions, and auxiliary subunits, including transmembrane AMPAR regulatory proteins (TARPs) located at the B' and D' positions, and cornichon homologues (CNIHs) or TARPs located at the A' and C' positions. Furthermore, we resolved the structure of the noelin (NOE1)-GluA1-GluA4 complex, in which NOE1 specifically binds to the GluA4 subunit at the B and D positions. Notably, NOE1 stabilizes the amino-terminal domain layer without affecting gating properties of the receptor. NOE1 contributes to AMPAR function by forming dimeric AMPAR assemblies that are likely to engage in extracellular networks, clustering receptors in synaptic environments and modulating receptor responsiveness to synaptic inputs. PubMed: 40550474DOI: 10.1038/s41586-025-09289-0 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.22 Å) |
Structure validation
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