8E97

PYD-106-bound Human GluN1a-GluN2C NMDA receptor in splayed conformation

8E97 の概要

• エントリーDOI: 10.2210/pdb8e97/pdb
• EMDBエントリー: 27953 27954 27955 27957 27958 27959 27960 27961
• 分子名称: Glutamate receptor ionotropic, NMDA 1, Glutamate receptor ionotropic, NMDA 2C, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: ligand-gated ion channel, ionotropic glutamate receptor, synaptic protein, transport protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 387285.20

構造登録者

Chou, T.-H.,Furukawa, H. (登録日: 2022-08-26, 公開日: 2022-12-07, 最終更新日: 2025-05-28)

主引用文献

Chou, T.H.,Kang, H.,Simorowski, N.,Traynelis, S.F.,Furukawa, H.
Structural insights into assembly and function of GluN1-2C, GluN1-2A-2C, and GluN1-2D NMDARs.
Mol.Cell, 82:4548-, 2022

PubMed Abstract: 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.

PubMed: 36309015
DOI: 10.1016/j.molcel.2022.10.008

実験手法

ELECTRON MICROSCOPY (4.19 Å)