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-Structure paper
| タイトル | Gating and noelin clustering of native Ca-permeable AMPA receptors. |
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| ジャーナル・号・ページ | Nature, Vol. 645, Issue 8080, Page 526-534, Year 2025 |
| 掲載日 | 2025年6月23日 |
著者 | Chengli Fang / Cathy J Spangler / Jumi Park / Natalie Sheldon / Laurence O Trussell / Eric Gouaux / ![]() |
| PubMed 要旨 | 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 ...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. |
リンク | Nature / PubMed:40550474 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 3.26 - 9.34 Å |
| 構造データ | ![]() EMDB-49711: Cryo-EM map of LBD-TMD combined from all cerebellar CP-AMPAR subtypes with 4 TARPs ![]() EMDB-49712: Cryo-EM map of LBD-TMD combined from all cerebellar CP-AMPAR subtypes with 2 TARPs ![]() EMDB-49713: Cryo-EM map of LBD-TMD combined from all cerebellar CP-AMPAR subtypes with 2 TARPs 2CNIHs ![]() EMDB-49714: Cryo-EM map of Noelin 1 with cerebellar GluA1/A4 ![]() EMDB-49715: Cryo-EM map of cerebellar GluA1/A4 with ordered ATD ![]() EMDB-49716: Cryo-EM map of cerebellar GluA1/A4 with disordered ATD ![]() EMDB-49717: Cryo-EM map of LBD-TMD in the active state combined from all cerebellar CP-AMPAR subtypes with 4 auxiliary proteins ![]() EMDB-49718: Cryo-EM map of cerebellar GluA1/A4 LBD-TMD in desensitized state ![]() EMDB-49719: Cryo-EM map of cerebellar GluA1/A4 LBD-TMD in Noelin-AMPAR complex in desensitized state ![]() EMDB-49720: Cryo-EM map of recombinant GluA4 with ordered ATD ![]() EMDB-49721: Cryo-EM map of recombinant GluA4 with disordered ATD ![]() EMDB-49722: Cryo-EM map of recombinant GluA4 with Noelin 1 EMDB-49723: The structure of Noelin 1 with GluA1/A4-ATD EMDB-49724, PDB-9nr7: EMDB-49725, PDB-9nr8: EMDB-49726, PDB-9nr9: EMDB-49727, PDB-9nra: |
| 化合物 | ![]() ChemComp-NAG: ![]() ChemComp-CA: ![]() ChemComp-ZK1: |
| 由来 |
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キーワード | MEMBRANE PROTEIN / iGluR / CP-AMPA receptors / Noelin 1 |
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