7YFH

Structure of the Rat GluN1-GluN2C NMDA receptor in complex with glycine, glutamate and (R)-PYD-106

7YFH の概要

• エントリーDOI: 10.2210/pdb7yfh/pdb
• EMDBエントリー: 33790
• 分子名称: Glutamate receptor ionotropic, NMDA 1, Glutamate receptor ionotropic, NMDA 2C, alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• 機能のキーワード: nmda receptor, glun2c, membrane protein
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 382434.85

構造登録者

Zhang, M.,Zhang, J.,Guo, F.,Li, Y.,Zhu, S. (登録日: 2022-07-08, 公開日: 2023-03-29, 最終更新日: 2024-11-20)

主引用文献

Zhang, J.,Zhang, M.,Wang, Q.,Wen, H.,Liu, Z.,Wang, F.,Wang, Y.,Yao, F.,Song, N.,Kou, Z.,Li, Y.,Guo, F.,Zhu, S.
Distinct structure and gating mechanism in diverse NMDA receptors with GluN2C and GluN2D subunits.
Nat.Struct.Mol.Biol., 30:629-639, 2023

PubMed Abstract: N-methyl-D-aspartate (NMDA) receptors are heterotetramers comprising two GluN1 and two alternate GluN2 (N2A-N2D) subunits. Here we report full-length cryo-EM structures of the human N1-N2D di-heterotetramer (di-receptor), rat N1-N2C di-receptor and N1-N2A-N2C tri-heterotetramer (tri-receptor) at a best resolution of 3.0 Å. The bilobate N-terminal domain (NTD) in N2D intrinsically adopts a closed conformation, leading to a compact NTD tetramer in the N1-N2D receptor. Additionally, crosslinking the ligand-binding domain (LBD) of two N1 protomers significantly elevated the channel open probability (Po) in N1-N2D di-receptors. Surprisingly, the N1-N2C di-receptor adopted both symmetric (minor) and asymmetric (major) conformations, the latter further locked by an allosteric potentiator, PYD-106, binding to a pocket between the NTD and LBD in only one N2C protomer. Finally, the N2A and N2C subunits in the N1-N2A-N2C tri-receptor display a conformation close to one protomer in the N1-N2A and N1-N2C di-receptors, respectively. These findings provide a comprehensive structural understanding of diverse function in major NMDA receptor subtypes.

PubMed: 36959261
DOI: 10.1038/s41594-023-00959-z

実験手法

ELECTRON MICROSCOPY (3 Å)