登録情報 データベース : EMDB / ID : EMD-32268 構造の表示 ダウンロードとリンクタイトル Cryo-EM structure of the ghrelin-bound human ghrelin receptor-Go complex マップデータ 詳細 試料複合体 : Cryo-EM structure of the ghrelin-bound human ghrelin receptor-Go complex複合体 : Guanine nucleotide-binding protein G(o) subunit alpha, Growth hormone secretagogue receptor type 1タンパク質・ペプチド : Guanine nucleotide-binding protein G(o) subunit alpha複合体 : Guanine nucleotide-binding proteinタンパク質・ペプチド : Growth hormone secretagogue receptor type 1タンパク質・ペプチド : Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2タンパク質・ペプチド : Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1複合体 : ScFv16複合体 : Appetite-regulating hormoneタンパク質・ペプチド : Appetite-regulating hormoneリガンド : CHOLESTEROL 詳細機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
growth hormone secretagogue receptor activity / regulation of hindgut contraction / ghrelin receptor binding / positive regulation of bone development / positive regulation of gastric mucosal blood circulation / regulation of growth hormone secretion / negative regulation of locomotion / growth hormone-releasing hormone receptor activity / cortisol secretion / positive regulation of small intestinal transit ... growth hormone secretagogue receptor activity / regulation of hindgut contraction / ghrelin receptor binding / positive regulation of bone development / positive regulation of gastric mucosal blood circulation / regulation of growth hormone secretion / negative regulation of locomotion / growth hormone-releasing hormone receptor activity / cortisol secretion / positive regulation of small intestinal transit / growth hormone-releasing hormone activity / negative regulation of circadian sleep/wake cycle, REM sleep / positive regulation of circadian sleep/wake cycle, non-REM sleep / negative regulation of locomotion involved in locomotory behavior / regulation of response to food / regulation of gastric motility / guanyl nucleotide binding / regulation of transmission of nerve impulse / gastric acid secretion / positive regulation of corticotropin secretion / response to follicle-stimulating hormone / positive regulation of cortisol secretion / growth hormone secretion / ghrelin secretion / positive regulation of growth rate / positive regulation of eating behavior / negative regulation of norepinephrine secretion / positive regulation of appetite / positive regulation of small intestine smooth muscle contraction / negative regulation of macrophage apoptotic process / adult feeding behavior / positive regulation of growth hormone secretion / negative regulation of appetite / positive regulation of growth hormone receptor signaling pathway / positive regulation of multicellular organism growth / actin polymerization or depolymerization / vesicle docking involved in exocytosis / cellular response to thyroid hormone stimulus / response to growth hormone / positive regulation of synapse assembly / cartilage development / positive regulation of insulin-like growth factor receptor signaling pathway / regulation of neurotransmitter receptor localization to postsynaptic specialization membrane / negative regulation of interleukin-1 beta production / response to food / positive regulation of vascular endothelial cell proliferation / cellular response to insulin-like growth factor stimulus / regulation of postsynapse organization / response to L-glutamate / regulation of synapse assembly / G protein-coupled dopamine receptor signaling pathway / regulation of heart contraction / positive regulation of fatty acid metabolic process / postsynaptic modulation of chemical synaptic transmission / protein tyrosine kinase activator activity / positive regulation of sprouting angiogenesis / response to dexamethasone / dendrite development / negative regulation of endothelial cell proliferation / positive regulation of insulin secretion involved in cellular response to glucose stimulus / peptide hormone binding / negative regulation of interleukin-6 production / negative regulation of tumor necrosis factor production / decidualization / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / Synthesis, secretion, and deacylation of Ghrelin / negative regulation of insulin secretion / G protein-coupled serotonin receptor binding / response to electrical stimulus / synapse assembly / positive regulation of adipose tissue development / excitatory postsynaptic potential / hormone-mediated signaling pathway / negative regulation of angiogenesis / Peptide ligand-binding receptors / insulin-like growth factor receptor signaling pathway / response to hormone / synaptic membrane / locomotory behavior / muscle contraction / G protein-coupled receptor binding / G protein-coupled receptor activity / Schaffer collateral - CA1 synapse / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G-protein activation / positive regulation of insulin secretion / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / ADP signalling through P2Y purinoceptor 12 類似検索 - 分子機能 Preproghrelin peptide / Growth hormone secretagogue receptor/motilin receptor / Motilin/ghrelin-associated peptide / Motilin/ghrelin / Motilin/ghrelin-associated peptide / Motilin/ghrelin / G-protein alpha subunit, group I / G-alpha domain profile. / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion ... Preproghrelin peptide / Growth hormone secretagogue receptor/motilin receptor / Motilin/ghrelin-associated peptide / Motilin/ghrelin / Motilin/ghrelin-associated peptide / Motilin/ghrelin / G-protein alpha subunit, group I / G-alpha domain profile. / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G protein alpha subunit / G-protein, gamma subunit / G-protein gamma subunit domain profile. / GGL domain / G-protein gamma-like domain superfamily / G-protein gamma-like domain / GGL domain / G protein gamma subunit-like motifs / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / G-protein coupled receptors family 1 signature. / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 7 transmembrane receptor (rhodopsin family) / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性 Guanine nucleotide-binding protein G(o) subunit alpha / Guanine nucleotide-binding protein G(o) subunit alpha / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Growth hormone secretagogue receptor type 1 / Appetite-regulating hormone 類似検索 - 構成要素生物種 Homo sapiens (ヒト) / synthetic construct (人工物) 手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 2.8 Å 詳細 データ登録者Qin J / Ming Q / Ji S / Mao C / Shen D / Zhang Y 資金援助 1件 詳細 詳細を隠すOrganization Grant number 国 Not funded
引用ジャーナル : Nat Commun / 年 : 2022タイトル : Molecular mechanism of agonism and inverse agonism in ghrelin receptor.著者 : Jiao Qin / Ye Cai / Zheng Xu / Qianqian Ming / Su-Yu Ji / Chao Wu / Huibing Zhang / Chunyou Mao / Dan-Dan Shen / Kunio Hirata / Yanbin Ma / Wei Yan / Yan Zhang / Zhenhua Shao / 要旨 : Much effort has been invested in the investigation of the structural basis of G protein-coupled receptors (GPCRs) activation. Inverse agonists, which can inhibit GPCRs with constitutive activity, are ... Much effort has been invested in the investigation of the structural basis of G protein-coupled receptors (GPCRs) activation. Inverse agonists, which can inhibit GPCRs with constitutive activity, are considered useful therapeutic agents, but the molecular mechanism of such ligands remains insufficiently understood. Here, we report a crystal structure of the ghrelin receptor bound to the inverse agonist PF-05190457 and a cryo-electron microscopy structure of the active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin. Our structures reveal a distinct binding mode of the inverse agonist PF-05190457 in the ghrelin receptor, different from the binding mode of agonists and neutral antagonists. Combining the structural comparisons and cellular function assays, we find that a polar network and a notable hydrophobic cluster are required for receptor activation and constitutive activity. Together, our study provides insights into the detailed mechanism of ghrelin receptor binding to agonists and inverse agonists, and paves the way to design specific ligands targeting ghrelin receptors. 履歴 登録 2021年11月24日 - ヘッダ(付随情報) 公開 2022年1月19日 - マップ公開 2022年1月19日 - 更新 2022年2月16日 - 現状 2022年2月16日 処理サイト : PDBj / 状態 : 公開
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