门控
受体
机制(生物学)
化学
生物物理学
物理
细胞生物学
蛋白质亚单位
NMDA受体
生物
生物化学
量子力学
基因
作者
Jilin Zhang,Ming Zhang,Qinrui Wang,Han Wen,Zheyi Liu,Fangjun Wang,Yuhang Wang,Fenyong Yao,Nan Song,Zhenhui Kou,Yang Li,Fei Guo,Shujia Zhu
标识
DOI:10.1038/s41594-023-00959-z
摘要
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI