EMD-33793
Structure of GluN1b-GluN2D NMDA receptor in complex with agonists glycine and glutamate.
EMD-33793
Single-particle5.1 Å
Deposition: 08/07/2022Map released: 29/03/2023
Last modified: 30/10/2024
Sample Organism:
Homo sapiens
Sample: NMDA receptor with NMDA 1 incorperated with NMDA 2D
Fitted models: 7yfm (Avg. Q-score: 0.309)
Deposition Authors: Zhang JL, Zhu SJ
,
Zhang M
Sample: NMDA receptor with NMDA 1 incorperated with NMDA 2D
Fitted models: 7yfm (Avg. Q-score: 0.309)
Deposition Authors: Zhang JL, Zhu SJ
,
Zhang M
Distinct structure and gating mechanism in diverse NMDA receptors with GluN2C and GluN2D subunits.
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
(2023) Nat Struct Mol Biol , 30 , 629 - 639
,
Wang Q,
Wen H ,
Liu Z,
Wang F,
Wang Y,
Yao F,
Song N,
Kou Z,
Li Y ,
Guo F,
Zhu S
(2023) Nat Struct Mol Biol , 30 , 629 - 639
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.
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.