登録情報 データベース : EMDB / ID : EMD-24267 構造の表示 ダウンロードとリンクタイトル Structures of human ghrelin receptor-Gi complexes with ghrelin and a synthetic agonist マップデータcryoEM map of GHSR-Gi-ghrelin 詳細 試料複合体 : Complex of GHSR-Gi-ghrelinタンパク質・ペプチド : Guanine nucleotide-binding protein G(i) subunit alpha-1タンパク質・ペプチド : Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-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 : Antibody fragmentタンパク質・ペプチド : Growth hormone secretagogue receptor type 1タンパク質・ペプチド : Ghrelin-27 残り2件を表示 表示を減らすリガンド : 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 / 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 small intestine smooth muscle contraction / positive regulation of appetite / 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 / 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 / response to food / negative regulation of interleukin-1 beta production / 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 / 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 / Synthesis, secretion, and deacylation of Ghrelin / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / negative regulation of insulin secretion / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / response to electrical stimulus / regulation of mitotic spindle organization / cellular response to forskolin / synapse assembly / positive regulation of adipose tissue development / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / hormone-mediated signaling pathway / negative regulation of angiogenesis / Peptide ligand-binding receptors / insulin-like growth factor receptor signaling pathway / excitatory postsynaptic potential / response to hormone / synaptic membrane / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / Schaffer collateral - CA1 synapse / 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 / positive regulation of insulin secretion / G-protein activation / 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 / response to peptide hormone 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(I)/G(S)/G(O) subunit gamma-2 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(i) subunit alpha-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) / Mus musculus (ハツカネズミ)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 2.7 Å 詳細 データ登録者Liu H / Sun D / Sun J / Zhang C 資金援助 米国, 2件 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) R35GM128641 米国 National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) R03TR003306 米国
引用ジャーナル : Nat Commun / 年 : 2021タイトル : Structural basis of human ghrelin receptor signaling by ghrelin and the synthetic agonist ibutamoren.著者 : Heng Liu / Dapeng Sun / Alexander Myasnikov / Marjorie Damian / Jean-Louis Baneres / Ji Sun / Cheng Zhang / 要旨 : The hunger hormone ghrelin activates the ghrelin receptor GHSR to stimulate food intake and growth hormone secretion and regulate reward signaling. Acylation of ghrelin at Ser3 is required for its ... The hunger hormone ghrelin activates the ghrelin receptor GHSR to stimulate food intake and growth hormone secretion and regulate reward signaling. Acylation of ghrelin at Ser3 is required for its agonistic action on GHSR. Synthetic agonists of GHSR are under clinical evaluation for disorders related to appetite and growth hormone dysregulation. Here, we report high-resolution cryo-EM structures of the GHSR-G signaling complex with ghrelin and the non-peptide agonist ibutamoren as an investigational new drug. Our structures together with mutagenesis data reveal the molecular basis for the binding of ghrelin and ibutamoren. Structural comparison suggests a salt bridge and an aromatic cluster near the agonist-binding pocket as important structural motifs in receptor activation. Notable structural variations of the G and GHSR coupling are observed in our cryo-EM analysis. Our results provide a framework for understanding GHSR signaling and developing new GHSR agonist drugs. 履歴 登録 2021年6月20日 - ヘッダ(付随情報) 公開 2021年12月15日 - マップ公開 2021年12月15日 - 更新 2021年12月15日 - 現状 2021年12月15日 処理サイト : RCSB / 状態 : 公開
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