Cryo-EM snapshots of NMDA receptor activation illuminate sequential rearrangements.

ABSTRACT: Canonical N-methyl-d-aspartate receptors (NMDARs) are glutamate-gated ion channels with critical roles in the development and function of the nervous system. The excitatory currents they produce reflect stochastic transitions between multiple agonist-bound closed- and open-pore states. We leveraged the intrinsically high open probability (P_o) of NMDARs composed of GluN1 and GluN2A subunits, together with judiciously chosen mutants and ligands, to achieve conditions in which receptors had a P_o near unity. Using single-particle cryo-electron microscopy (cryo-EM), we captured three activated receptor states, each with distinct conformations of the gate-forming M3 helices. Separately, we carried out single-channel electrophysiology, together with stat

SUBMITTER: Abbott JA 

PROVIDER: S-EPMC12459464 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature