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-Structure paper
タイトル | Structural insights into assembly and function of GluN1-2C, GluN1-2A-2C, and GluN1-2D NMDARs. |
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ジャーナル・号・ページ | Mol Cell, Vol. 82, Issue 23, Page 4548-44563.e4, Year 2022 |
掲載日 | 2022年12月1日 |
著者 | Tsung-Han Chou / Hyunook Kang / Noriko Simorowski / Stephen F Traynelis / Hiro Furukawa / |
PubMed 要旨 | Neurotransmission mediated by diverse subtypes of N-methyl-D-aspartate receptors (NMDARs) is fundamental for basic brain functions and development as well as neuropsychiatric diseases and disorders. ...Neurotransmission mediated by diverse subtypes of N-methyl-D-aspartate receptors (NMDARs) is fundamental for basic brain functions and development as well as neuropsychiatric diseases and disorders. NMDARs are glycine- and glutamate-gated ion channels that exist as heterotetramers composed of obligatory GluN1 and GluN2(A-D) and/or GluN3(A-B). The GluN2C and GluN2D subunits form ion channels with distinct properties and spatio-temporal expression patterns. Here, we provide the structures of the agonist-bound human GluN1-2C NMDAR in the presence and absence of the GluN2C-selective positive allosteric potentiator (PAM), PYD-106, the agonist-bound GluN1-2A-2C tri-heteromeric NMDAR, and agonist-bound GluN1-2D NMDARs by single-particle electron cryomicroscopy. Our analysis shows unique inter-subunit and domain arrangements of the GluN2C NMDARs, which contribute to functional regulation and formation of the PAM binding pocket and is distinct from GluN2D NMDARs. Our findings here provide the fundamental blueprint to study GluN2C- and GluN2D-containing NMDARs, which are uniquely involved in neuropsychiatric disorders. |
リンク | Mol Cell / PubMed:36309015 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.26 - 4.24 Å |
構造データ | EMDB-27953, PDB-8e92: EMDB-27954, PDB-8e93: EMDB-27955, PDB-8e94: EMDB-27957, PDB-8e96: EMDB-27958, PDB-8e97: EMDB-27959, PDB-8e98: EMDB-27960: D-cycloserine and glutamate bound Human GluN1a-GluN2C NMDA receptor in nanodisc - splayed conformation EMDB-27961, PDB-8e99: EMDB-28051: Local refined map of the LBD region of Human GluN1a-GluN2D NMDA receptor EMDB-28052: Local refined map of ATD region of GluN1a-2D complex EMDB-28053: Local refined map of the TMD region of Human GluN1a-GluN2D NMDA receptor |
化合物 | ChemComp-NAG: ChemComp-IWB: ChemComp-GLY: ChemComp-GLU: |
由来 |
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キーワード | TRANSPORT PROTEIN / Ligand-gated ion channel / ionotropic glutamate receptor / synaptic protein / voltage-gate ion channel / TRANSPORT PROTEIN/IMMUNE SYSTEM / TRANSPORT PROTEIN-IMMUNE SYSTEM complex |