9D3A
Nonactive state of Gly-,Glu- bound GluN1a-2B-2D NMDAR (Low-res)
Summary for 9D3A
| Entry DOI | 10.2210/pdb9d3a/pdb |
| EMDB information | 46529 |
| Descriptor | Glutamate receptor ionotropic, NMDA 1, Glutamate receptor ionotropic, NMDA 2B, Glutamate receptor ionotropic, NMDA 2D, ... (7 entities in total) |
| Functional Keywords | n-methyl-d-aspartate receptor, nonactive, glun2b, glun2d, membrane protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 379880.06 |
| Authors | Hyunook, K.,Hiro, F. (deposition date: 2024-08-09, release date: 2025-02-26, Last modification date: 2025-04-16) |
| Primary citation | Kang, H.,Epstein, M.,Banke, T.G.,Perszyk, R.,Simorowski, N.,Paladugu, S.,Liotta, D.C.,Traynelis, S.F.,Furukawa, H. Structural basis for channel gating and blockade in tri-heteromeric GluN1-2B-2D NMDA receptor. Neuron, 113:991-, 2025 Cited by PubMed Abstract: Discrete activation of N-methyl-D-aspartate receptor (NMDAR) subtypes by glutamate and the co-agonist glycine is fundamental to neuroplasticity. A distinct variant, the tri-heteromeric receptor, comprising glycine-binding GluN1 and two types of glutamate-binding GluN2 subunits, exhibits unique pharmacological characteristics, notably enhanced sensitivity to the anti-depressant channel blocker S-(+)-ketamine. Despite its significance, the structural mechanisms underlying ligand gating and channel blockade of tri-heteromeric NMDARs remain poorly understood. Here, we identify and characterize tri-heteromeric GluN1-2B-2D NMDAR in the adult brain, resolving its structures in the activated, inhibited, and S-(+)-ketamine-blocked states. These structures reveal the ligand-dependent conformational dynamics that modulate the tension between the extracellular domain and transmembrane channels, governing channel gating and blockade. Additionally, we demonstrate that the inhibitor (S)-DQP-997-74 selectively decouples linker tension in GluN2D, offering insights into subtype-selective targeting for cognitive modulation. PubMed: 39954679DOI: 10.1016/j.neuron.2025.01.013 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.78 Å) |
Structure validation
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