9OEH
GluN1/GluN3A in complex with CGP and DCKA
Summary for 9OEH
| Entry DOI | 10.2210/pdb9oeh/pdb |
| EMDB information | 70399 |
| Descriptor | Isoform E of Glutamate receptor ionotropic, NMDA 1, Glutamate receptor ionotropic, NMDA 3A, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total) |
| Functional Keywords | ligand-gated ion channel, nmda, inhibitor, transport protein |
| Biological source | Rattus norvegicus (Norway rat) More |
| Total number of polymer chains | 4 |
| Total formula weight | 415240.92 |
| Authors | Kim, J.,Gouaux, E. (deposition date: 2025-04-28, release date: 2026-08-26, Last modification date: 2026-10-14) |
| Primary citation | Kim, J.,Benton, A.J.,Lotti, J.S.,Rouzbeh, N.,Hansen, K.B.,Gouaux, E. Structural and mechanistic insights into gating and allosteric modulation of GluN1-GluN3A NMDA receptors. Nat.Struct.Mol.Biol., 33:1299-1310, 2026 Cited by PubMed Abstract: N-methyl-D-aspartate receptors (NMDARs) mediate excitatory signaling essential for synaptic plasticity and memory. Unlike GluN2-containing NMDARs, GluN3-containing receptors are activated solely by glycine and exhibit profound desensitization and paradoxical potentiation by GluN1-selective antagonists, including CGP-78608 (CGP). Although GluN3A-containing NMDARs regulate synapse pruning and excitotoxicity, and are associated with schizophrenia, autism and stroke, their native stoichiometry and gating mechanism are poorly defined. Here, using single-molecule pull-down analysis, we show that native GluN3A-containing receptors are diheteromeric assemblies. Cryogenic-electron microscopy analysis of GluN1-GluN3A receptors in antagonist-bound, preactive, active and desensitized states, augmented by electrophysiology and pharmacology experiments, show how glycine activates the receptor solely via GluN3A-dependent conformational changes, opening the gate with two-fold symmetry, and induces a roughly four-fold symmetric desensitized state. CGP-bound GluN1 restricts GluN3A rotation, promoting glycine-induced activation by blocking desensitization. These findings illuminate how CGP potentiates GluN1-GluN3A receptor activity, place the receptor gating mechanism on a structural foundation and define the molecular basis for pharmacological modulation. PubMed: 42665662DOI: 10.1038/s41594-026-01866-9 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.67 Å) |
Structure validation
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