9C7P
Diheteromeric GluN1/GluN2A (delM653) in digitonin complexed with glycine, glutamate, and GNE-4123
Summary for 9C7P
| Entry DOI | 10.2210/pdb9c7p/pdb |
| EMDB information | 45283 |
| Descriptor | Glutamate receptor ionotropic, NMDA 1, Green fluorescent protein chimera, Glutamate receptor ionotropic, NMDA 2A, Green fluorescent protein chimera (2 entities in total) |
| Functional Keywords | ion channel, nmda, positive allosteric modulator, pre-open pore conformation, transport protein |
| Biological source | Rattus norvegicus (Norway rat) More |
| Total number of polymer chains | 4 |
| Total formula weight | 502230.80 |
| Authors | Jalali-Yazdi, F.,Kim, J.,Gouaux, E. (deposition date: 2024-06-10, release date: 2025-09-24, Last modification date: 2026-02-04) |
| Primary citation | Abbott, J.A.,Kim, J.,Liu, B.,Popescu, G.K.,Gouaux, E.,Jalali-Yazdi, F. Cryo-EM snapshots of NMDA receptor activation illuminate sequential rearrangements. Sci Adv, 11:eadx4647-eadx4647, 2025 Cited by PubMed Abstract: Canonical -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 () of NMDARs composed of GluN1 and GluN2A subunits, together with judiciously chosen mutants and ligands, to achieve conditions in which receptors had a 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 statistical modeling, to relate the cryo-EM structures to the gating reaction. NMDAR channel opening involves bending of the pore-forming M3 helices to produce a transient open-channel conformation, subsequently stabilized by new interactions between the D2-M3 linkers with the pre-M1 helices and the pre-M4 loops, to yield the stable open channel. PubMed: 40991709DOI: 10.1126/sciadv.adx4647 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.61 Å) |
Structure validation
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