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	Ligand and G-protein selectivity in the κ-opioid receptor.
ジャーナル・号・ページ	Nature, Vol. 617, Issue 7960, Page 417-425, Year 2023
掲載日	2023年5月3日
著者	Jianming Han / Jingying Zhang / Antonina L Nazarova / Sarah M Bernhard / Brian E Krumm / Lei Zhao / Jordy Homing Lam / Vipin A Rangari / Susruta Majumdar / David E Nichols / Vsevolod Katritch / Peng Yuan / Jonathan F Fay / Tao Che /
PubMed 要旨	The κ-opioid receptor (KOR) represents a highly desirable therapeutic target for treating not only pain but also addiction and affective disorders. However, the development of KOR analgesics has ...The κ-opioid receptor (KOR) represents a highly desirable therapeutic target for treating not only pain but also addiction and affective disorders. However, the development of KOR analgesics has been hindered by the associated hallucinogenic side effects. The initiation of KOR signalling requires the G-family proteins including the conventional (G, G, G, G and G) and nonconventional (G and G) subtypes. How hallucinogens exert their actions through KOR and how KOR determines G-protein subtype selectivity are not well understood. Here we determined the active-state structures of KOR in a complex with multiple G-protein heterotrimers-G, G, G and G-using cryo-electron microscopy. The KOR-G-protein complexes are bound to hallucinogenic salvinorins or highly selective KOR agonists. Comparisons of these structures reveal molecular determinants critical for KOR-G-protein interactions as well as key elements governing G-family subtype selectivity and KOR ligand selectivity. Furthermore, the four G-protein subtypes display an intrinsically different binding affinity and allosteric activity on agonist binding at KOR. These results provide insights into the actions of opioids and G-protein-coupling specificity at KOR and establish a foundation to examine the therapeutic potential of pathway-selective agonists of KOR.
リンク	Nature / PubMed:37138078 / PubMed Central
手法	EM (単粒子)
解像度	2.61 - 2.82 Å
構造データ	27804 8dzp EMDB-27804, PDB-8dzp: momSalB bound Kappa Opioid Receptor in complex with Gi1 手法: EM (単粒子) / 解像度: 2.71 Å 27805 8dzq EMDB-27805, PDB-8dzq: momSalB bound Kappa Opioid Receptor in complex with GoA 手法: EM (単粒子) / 解像度: 2.82 Å 27806 8dzr EMDB-27806, PDB-8dzr: GR89,696 bound Kappa Opioid Receptor in complex with gustducin 手法: EM (単粒子) / 解像度: 2.61 Å 27807 8dzs EMDB-27807, PDB-8dzs: GR89,696 bound Kappa Opioid Receptor in complex with Gz 手法: EM (単粒子) / 解像度: 2.65 Å EMDB-41876: momSalB bound Kappa Opioid Receptor in complex with GoA 手法: EM (単粒子) / 解像度: 2.8 Å EMDB-43732: momSalB bound Kappa Opioid Receptor in complex Gi1 手法: EM (単粒子) / 解像度: 2.71 Å EMDB-43733: GR89,696 bound Kappa Opioid Receptor in complex with Gz 手法: EM (単粒子) / 解像度: 2.73 Å EMDB-43734: GR89,696 bound Kappa Opioid Receptor in complex with gustducin 手法: EM (単粒子) / 解像度: 2.72 Å
化合物	ChemComp-U99: methyl (2S,4aR,6aR,7R,9S,10aS,10bR)-2-(furan-3-yl)-9-(methoxymethoxy)-6a,10b-dimethyl-4,10-dioxododecahydro-2H-naphtho[2,1-c]pyran-7-carboxylate ChemComp-U9I: methyl (3R)-4-[(3,4-dichlorophenyl)acetyl]-3-[(pyrrolidin-1-yl)methyl]piperazine-1-carboxylate / (3R)-3β-[(ピロリジン-1-イル)メチル]-4-[(3,4-ジクロロフェニル)アセチル]ピペラジン-1-カルボ(以下略)
由来	homo sapiens (ヒト) mus musculus (ハツカネズミ)
キーワード	MEMBRANE PROTEIN / GPCR / KAPPA OPIOID Receptor / SALVINORIN / Receptor / Kappa / KOR / Opioid / G protein