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-Structure paper
タイトル | Structure and function of GluN1-3A NMDA receptor excitatory glycine receptor channel. |
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ジャーナル・号・ページ | Sci Adv, Vol. 10, Issue 15, Page eadl5952, Year 2024 |
掲載日 | 2024年4月12日 |
著者 | Kevin Michalski / Hiro Furukawa / |
PubMed 要旨 | -methyl-d-aspartate receptors (NMDARs) and other ionotropic glutamate receptors (iGluRs) mediate most of the excitatory signaling in the mammalian brains in response to the neurotransmitter glutamate. ...-methyl-d-aspartate receptors (NMDARs) and other ionotropic glutamate receptors (iGluRs) mediate most of the excitatory signaling in the mammalian brains in response to the neurotransmitter glutamate. Uniquely, NMDARs composed of GluN1 and GluN3 are activated exclusively by glycine, the neurotransmitter conventionally mediating inhibitory signaling when it binds to pentameric glycine receptors. The GluN1-3 NMDARs are vital for regulating neuronal excitability, circuit function, and specific behaviors, yet our understanding of their functional mechanism at the molecular level has remained limited. Here, we present cryo-electron microscopy structures of GluN1-3A NMDARs bound to an antagonist, CNQX, and an agonist, glycine. The structures show a 1-3-1-3 subunit heterotetrameric arrangement and an unprecedented pattern of GluN3A subunit orientation shift between the glycine-bound and CNQX-bound structures. Site-directed disruption of the unique subunit interface in the glycine-bound structure mitigated desensitization. Our study provides a foundation for understanding the distinct structural dynamics of GluN3 that are linked to the unique function of GluN1-3 NMDARs. |
リンク | Sci Adv / PubMed:38598639 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.96 - 4.23 Å |
構造データ | EMDB-42520, PDB-8usw: EMDB-42522, PDB-8usx: EMDB-42580, PDB-8uue: |
化合物 |
ChemComp-DQC: |
由来 |
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キーワード | MEMBRANE PROTEIN / Channel / receptor |