6WI1
GluN1b-GluN2B NMDA receptor in active conformation stabilized by inter-GluN1b-GluN2B subunit cross-linking
Summary for 6WI1
| Entry DOI | 10.2210/pdb6wi1/pdb |
| EMDB information | 21682 |
| Descriptor | Ionotropic glutamate receptor , NMDA receptor GluN1b, Ionotropic glutamate receptor , NMDA receptor GluN2B, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total) |
| Functional Keywords | nmdars, ligand-gated ion channels, metal transport, ionotropic glutamate receptor, membrane protein |
| Biological source | Rattus norvegicus (Rat) More |
| Total number of polymer chains | 4 |
| Total formula weight | 396708.58 |
| Authors | Chou, T.,Tajima, N.,Furukawa, H. (deposition date: 2020-04-08, release date: 2020-07-15, Last modification date: 2024-10-30) |
| Primary citation | Chou, T.H.,Tajima, N.,Romero-Hernandez, A.,Furukawa, H. Structural Basis of Functional Transitions in Mammalian NMDA Receptors. Cell, 182:357-371.e13, 2020 Cited by PubMed Abstract: Excitatory neurotransmission meditated by glutamate receptors including N-methyl-D-aspartate receptors (NMDARs) is pivotal to brain development and function. NMDARs are heterotetramers composed of GluN1 and GluN2 subunits, which bind glycine and glutamate, respectively, to activate their ion channels. Despite importance in brain physiology, the precise mechanisms by which activation and inhibition occur via subunit-specific binding of agonists and antagonists remain largely unknown. Here, we show the detailed patterns of conformational changes and inter-subunit and -domain reorientation leading to agonist-gating and subunit-dependent competitive inhibition by providing multiple structures in distinct ligand states at 4 Å or better. The structures reveal that activation and competitive inhibition by both GluN1 and GluN2 antagonists occur by controlling the tension of the linker between the ligand-binding domain and the transmembrane ion channel of the GluN2 subunit. Our results provide detailed mechanistic insights into NMDAR pharmacology, activation, and inhibition, which are fundamental to the brain physiology. PubMed: 32610085DOI: 10.1016/j.cell.2020.05.052 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.62 Å) |
Structure validation
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