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
positive regulation of bone development / positive regulation of gastric mucosal blood circulation / ghrelin receptor binding / negative regulation of locomotion / cortisol secretion / growth hormone secretagogue receptor activity / regulation of hindgut contraction / growth hormone-releasing hormone activity / negative regulation of circadian sleep/wake cycle, REM sleep / regulation of growth hormone secretion ... positive regulation of bone development / positive regulation of gastric mucosal blood circulation / ghrelin receptor binding / negative regulation of locomotion / cortisol secretion / growth hormone secretagogue receptor activity / regulation of hindgut contraction / growth hormone-releasing hormone activity / negative regulation of circadian sleep/wake cycle, REM sleep / regulation of growth hormone secretion / positive regulation of small intestinal transit / regulation of response to food / negative regulation of locomotion involved in locomotory behavior / growth hormone-releasing hormone receptor activity / regulation of gastric motility / response to follicle-stimulating hormone / regulation of transmission of nerve impulse / positive regulation of circadian sleep/wake cycle, non-REM sleep / positive regulation of cortisol secretion / positive regulation of corticotropin secretion / positive regulation of growth rate / ghrelin secretion / gastric acid secretion / positive regulation of appetite / growth hormone secretion / negative regulation of norepinephrine secretion / positive regulation of small intestine smooth muscle contraction / negative regulation of macrophage apoptotic process / neuronal dense core vesicle lumen / positive regulation of eating behavior / adult feeding behavior / positive regulation of growth hormone secretion / positive regulation of growth hormone receptor signaling pathway / negative regulation of appetite / actin polymerization or depolymerization / positive regulation of multicellular organism growth / cellular response to thyroid hormone stimulus / cartilage development / response to growth hormone / regulation of postsynapse organization / positive regulation of insulin-like growth factor receptor signaling pathway / response to L-glutamate / positive regulation of synapse assembly / positive regulation of vascular endothelial cell proliferation / negative regulation of interleukin-1 beta production / response to food / positive regulation of fatty acid metabolic process / cellular response to insulin-like growth factor stimulus / response to dexamethasone / regulation of synapse assembly / positive regulation of sprouting angiogenesis / regulation of neurotransmitter receptor localization to postsynaptic specialization membrane / negative regulation of endothelial cell proliferation / dendrite development / negative regulation of interleukin-6 production / peptide hormone binding / decidualization / protein tyrosine kinase activator activity / negative regulation of tumor necrosis factor production / response to electrical stimulus / Synthesis, secretion, and deacylation of Ghrelin / positive regulation of insulin secretion involved in cellular response to glucose stimulus / postsynaptic modulation of chemical synaptic transmission / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / T cell migration / Adenylate cyclase inhibitory pathway / synapse assembly / response to hormone / D2 dopamine receptor binding / response to prostaglandin E / hormone-mediated signaling pathway / positive regulation of adipose tissue development / adenylate cyclase regulator activity / G protein-coupled serotonin receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / cellular response to forskolin / insulin-like growth factor receptor signaling pathway / regulation of mitotic spindle organization / synaptic membrane / negative regulation of angiogenesis / Peptide ligand-binding receptors / excitatory postsynaptic potential / Regulation of insulin secretion / positive regulation of cholesterol biosynthetic process / negative regulation of insulin secretion / G protein-coupled receptor activity / G protein-coupled receptor binding / response to peptide hormone / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / positive regulation of insulin secretion / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / negative regulation of inflammatory response / centriolar satellite / G-protein beta/gamma-subunit complex binding / Schaffer collateral - CA1 synapse / response to estrogen / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta 類似検索 - 分子機能 Preproghrelin peptide / Motilin/ghrelin-associated peptide / Motilin/ghrelin / Motilin/ghrelin-associated peptide / Motilin/ghrelin / Growth hormone secretagogue receptor/motilin receptor / G-protein alpha subunit, group I / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit ... Preproghrelin peptide / Motilin/ghrelin-associated peptide / Motilin/ghrelin / Motilin/ghrelin-associated peptide / Motilin/ghrelin / Growth hormone secretagogue receptor/motilin receptor / G-protein alpha subunit, group I / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G-alpha domain profile. / G protein alpha subunit / G-protein, gamma subunit / G-protein gamma subunit domain profile. / G-protein gamma-like domain / G-protein gamma-like domain superfamily / GGL domain / G protein gamma subunit-like motifs / GGL domain / G protein beta WD-40 repeat protein / 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. / 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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