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	Kainate receptor channel opening and gating mechanism.
Journal, issue, pages	Nature, Year 2024
Publish date	May 22, 2024
Authors	Shanti Pal Gangwar / Maria V Yelshanskaya / Kirill D Nadezhdin / Laura Y Yen / Thomas P Newton / Muhammed Aktolun / Maria G Kurnikova / Alexander I Sobolevsky /
PubMed Abstract	Kainate receptors, a subclass of ionotropic glutamate receptors, are tetrameric ligand-gated ion channels that mediate excitatory neurotransmission. Kainate receptors modulate neuronal circuits and ...Kainate receptors, a subclass of ionotropic glutamate receptors, are tetrameric ligand-gated ion channels that mediate excitatory neurotransmission. Kainate receptors modulate neuronal circuits and synaptic plasticity during the development and function of the central nervous system and are implicated in various neurological and psychiatric diseases, including epilepsy, depression, schizophrenia, anxiety and autism. Although structures of kainate receptor domains and subunit assemblies are available, the mechanism of kainate receptor gating remains poorly understood. Here we present cryo-electron microscopy structures of the kainate receptor GluK2 in the presence of the agonist glutamate and the positive allosteric modulators lectin concanavalin A and BPAM344. Concanavalin A and BPAM344 inhibit kainate receptor desensitization and prolong activation by acting as a spacer between the amino-terminal and ligand-binding domains and a stabilizer of the ligand-binding domain dimer interface, respectively. Channel opening involves the kinking of all four pore-forming M3 helices. Our structures reveal the molecular basis of kainate receptor gating, which could guide the development of drugs for treatment of neurological disorders.
External links	Nature / PubMed:38778115
Methods	EM (single particle)
Resolution	3.36 - 6.66 Å
Structure data	EMDB-44123: Cryo-EM density of GluK2 amino-terminal domain (GluK2-ATD) from the open-state structure of kainate receptor GluK2 in complex with agonist glutamate and positive allosteric modulator BPAM344 bound to ConA Method: EM (single particle) / Resolution: 3.5 Å 44124 9b33 EMDB-44124, PDB-9b33: Structure of concanavalin A (ConA) dimer from the open-state structure of kainate receptor GluK2 in complex with agonist glutamate and positive allosteric modulator BPAM344 bound to one ConA dimer. Type II interface between GluK2 ligand-binding domain and ConA Method: EM (single particle) / Resolution: 4.07 Å 44125 9b34 EMDB-44125, PDB-9b34: Structure of concanavalin A (ConA) dimer from the open-state structure of kainate receptor GluK2 in complex with agonist glutamate and positive allosteric modulator BPAM344 bound to two ConA dimers. Type I interface between GluK2 ligand-binding domain and ConA Method: EM (single particle) / Resolution: 3.58 Å EMDB-44126: Open state of kainate receptor GluK2 in complex with agonist glutamate and positive allosteric modulator BPAM344 bound to two concanavalin A dimers Method: EM (single particle) / Resolution: 4.29 Å EMDB-44127: Open state of kainate receptor GluK2 in complex with agonist glutamate and positive allosteric modulator BPAM344 bound to one concanavalin A dimer Method: EM (single particle) / Resolution: 6.66 Å 44128 9b35 EMDB-44128, PDB-9b35: Ligand-binding and transmembrane domains of kainate receptor GluK2 in the open state, a complex with agonist glutamate and positive allosteric modulator BPAM344 Method: EM (single particle) / Resolution: 3.4 Å 44129 9b36 EMDB-44129, PDB-9b36: Open state of kainate receptor GluK2 in complex with agonist glutamate and positive allosteric modulator BPAM344 bound to two concanavalin A dimers. Composite map. Method: EM (single particle) / Resolution: 4.29 Å 44130 9b37 EMDB-44130, PDB-9b37: Open state of kainate receptor GluK2 in complex with agonist glutamate and positive allosteric modulator BPAM344 bound to one concanavalin A dimer. Composite map. Method: EM (single particle) / Resolution: 6.66 Å 44131 9b38 EMDB-44131, PDB-9b38: Kainate receptor GluK2 in complex with agonist glutamate with pseudo 4-fold symmetrical ligand-binding domain layer Method: EM (single particle) / Resolution: 3.36 Å 44132 9b39 EMDB-44132, PDB-9b39: Kainate receptor GluK2 in complex with agonist glutamate with asymmetric ligand-binding domain layer Method: EM (single particle) / Resolution: 3.84 Å
Chemicals	ChemComp-ZN: Unknown entry ChemComp-CA: Unknown entry ChemComp-GLU: GLUTAMIC ACID / Glutamic acid ChemComp-2J9: 4-cyclopropyl-7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide ChemComp-POV: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / phospholipidYM / POPC ChemComp-CLR: CHOLESTEROL / Cholesterol ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine ChemComp-MAN*: alpha-D-mannopyranose / Mannose
Source	rattus norvegicus (Norway rat) canavalia ensiformis (jack bean)
Keywords	MEMBRANE PROTEIN / kainate receptor / GluK2 / positive allosteric modulator / BPAM344 / open / concanavalin A / ConA / glutamate / LBD-TMD / ligand-binding domain / transmembrane domain / pseudo 4-fold symmetrical / LBD / asymmetric