EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Kainate receptor channel opening and gating mechanism.
ジャーナル・号・ページ	Nature, Vol. 630, Issue 8017, Page 762-768, Year 2024
掲載日	2024年5月22日
著者	Shanti Pal Gangwar / Maria V Yelshanskaya / Kirill D Nadezhdin / Laura Y Yen / Thomas P Newton / Muhammed Aktolun / Maria G Kurnikova / Alexander I Sobolevsky /
PubMed 要旨	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.
リンク	Nature / PubMed:38778115 / PubMed Central
手法	EM (単粒子)
解像度	3.36 - 6.66 Å
構造データ	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 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 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. 手法: EM (単粒子) / 解像度: 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. 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 3.36 Å 44132 9b39 EMDB-44132, PDB-9b39: Kainate receptor GluK2 in complex with agonist glutamate with asymmetric ligand-binding domain layer 手法: EM (単粒子) / 解像度: 3.84 Å
化合物	ChemComp-ZN: Unknown entry ChemComp-CA: Unknown entry / カルシウムジカチオン ChemComp-GLU: GLUTAMIC ACID / グルタミン酸 ChemComp-2J9: 4-cyclopropyl-7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide / 3,4-ジヒドロ-4-シクロプロピル-7-フルオロ-2H-1,2,4-ベンゾチアジアジン1,1-ジオキシド ChemComp-POV: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / リン脂質YM ChemComp-CLR: CHOLESTEROL / コレステロ-ル ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン ChemComp-MAN*: alpha-D-mannopyranose / α-D-マンノピラノ-ス
由来	rattus norvegicus (ドブネズミ) canavalia ensiformis (タチナタマメ)
キーワード	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