Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Molecular mechanism of ligand gating and opening of NMDA receptor.
Journal, issue, pages	Nature, Vol. 632, Issue 8023, Page 209-217, Year 2024
Publish date	Jul 31, 2024
Authors	Tsung-Han Chou / Max Epstein / Russell G Fritzemeier / Nicholas S Akins / Srinu Paladugu / Elijah Z Ullman / Dennis C Liotta / Stephen F Traynelis / Hiro Furukawa /
PubMed Abstract	Glutamate transmission and activation of ionotropic glutamate receptors are the fundamental means by which neurons control their excitability and neuroplasticity. The N-methyl-D-aspartate receptor ...Glutamate transmission and activation of ionotropic glutamate receptors are the fundamental means by which neurons control their excitability and neuroplasticity. The N-methyl-D-aspartate receptor (NMDAR) is unique among all ligand-gated channels, requiring two ligands-glutamate and glycine-for activation. These receptors function as heterotetrameric ion channels, with the channel opening dependent on the simultaneous binding of glycine and glutamate to the extracellular ligand-binding domains (LBDs) of the GluN1 and GluN2 subunits, respectively. The exact molecular mechanism for channel gating by the two ligands has been unclear, particularly without structures representing the open channel and apo states. Here we show that the channel gate opening requires tension in the linker connecting the LBD and transmembrane domain (TMD) and rotation of the extracellular domain relative to the TMD. Using electron cryomicroscopy, we captured the structure of the GluN1-GluN2B (GluN1-2B) NMDAR in its open state bound to a positive allosteric modulator. This process rotates and bends the pore-forming helices in GluN1 and GluN2B, altering the symmetry of the TMD channel from pseudofourfold to twofold. Structures of GluN1-2B NMDAR in apo and single-liganded states showed that binding of either glycine or glutamate alone leads to distinct GluN1-2B dimer arrangements but insufficient tension in the LBD-TMD linker for channel opening. This mechanistic framework identifies a key determinant for channel gating and a potential pharmacological strategy for modulating NMDAR activity.
External links	Nature / PubMed:39085540 / PubMed Central
Methods	EM (single particle)
Resolution	3.13 - 4.05 Å
Structure data	43779 9are EMDB-43779, PDB-9are: Rat GluN1-GluN2B NMDA receptor channel in complex with glycine, glutamate, and EU-1622-A, in open-channel conformation Method: EM (single particle) / Resolution: 3.72 Å 43780 9arf EMDB-43780, PDB-9arf: Rat GluN1-GluN2B NMDA receptor channel in complex with glycine, glutamate, and EU-1622-A, in nonactive1 conformation Method: EM (single particle) / Resolution: 3.13 Å 43781 9arg EMDB-43781, PDB-9arg: Rat GluN1-GluN2B NMDA receptor channel in apo conformation Method: EM (single particle) / Resolution: 4.05 Å 43782 9arh EMDB-43782, PDB-9arh: Rat GluN1-GluN2B NMDA receptor channel in complex with glycine Method: EM (single particle) / Resolution: 3.69 Å 43783 9ari EMDB-43783, PDB-9ari: Rat GluN1-GluN2B NMDA receptor channel in complex with glutamate Method: EM (single particle) / Resolution: 3.9 Å 44586 9bib EMDB-44586, PDB-9bib: Rat GluN1-GluN2B NMDA receptor channel in complex with glycine, glutamate, and EU-1622-A, in open-channel conformation, C1 symmetry Method: EM (single particle) / Resolution: 3.81 Å
Chemicals	ChemComp-GLY: GLYCINE ChemComp-GLU: GLUTAMIC ACID ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose
Source	rattus norvegicus (Norway rat)
Keywords	MEMBRANE PROTEIN / Ligand-gated ion channel / ionotropic glutamate receptor / synaptic membrane protein / Ion channel