6USU
Crystal structure of GluN1/GluN2A ligand-binding domain in complex with L689,560 and glutamate
Summary for 6USU
| Entry DOI | 10.2210/pdb6usu/pdb |
| Descriptor | Glutamate receptor ionotropic, NMDA 1, Glutamate receptor ionotropic, NMDA 2A, (2R,4S)-5,7-dichloro-4-[(phenylcarbamoyl)amino]-1,2,3,4-tetrahydroquinoline-2-carboxylic acid, ... (5 entities in total) |
| Functional Keywords | nmdars, lbd, ion channels, metal transport |
| Biological source | Rattus norvegicus (Rat) More |
| Total number of polymer chains | 2 |
| Total formula weight | 65652.68 |
| Authors | Romero-Hernandez, A.,Tajima, N.,Chou, T.,Furukawa, H. (deposition date: 2019-10-28, release date: 2020-07-15, Last modification date: 2024-10-23) |
| Primary citation | Chou, T.H.,Tajima, N.,Romero-Hernandez, A.,Furukawa, H. Structural Basis of Functional Transitions in Mammalian NMDA Receptors. Cell, 182:357-, 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 | X-RAY DIFFRACTION (2.092 Å) |
Structure validation
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