登録情報 データベース : EMDB / ID : EMD-20190 構造の表示 ダウンロードとリンクタイトル Structure of human Smoothened-Gi complex マップデータSmoothened-Gi complex 詳細 試料複合体 : Smoothened-Gi-Fab complex複合体 : Smoothened homologタンパク質・ペプチド : Smoothened homolog複合体 : Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, 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) 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複合体 : Fab light chain, Fab heavy chainタンパク質・ペプチド : Fab light chainタンパク質・ペプチド : Fab heavy chainリガンド : 17-[3-(3,3-DIMETHYL-OXIRANYL)-1-METHYL-PROPYL]-10,13-DIMETHYL-2,3,4,7,8,9,10,11,12,13,14,15,16,17-TETRADECAHYDRO-1H-CYC LOPENTA[A]PHENANTHREN-3-OL 詳細 キーワード GPCR / Complex / Hedgehog signaling / SIGNALING PROTEIN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
ventral midline determination / mesenchymal to epithelial transition involved in metanephric renal vesicle formation / response to inositol / regulation of heart morphogenesis / contact inhibition / negative regulation of hair follicle development / central nervous system neuron differentiation / 9+0 non-motile cilium / pancreas morphogenesis / regulation of somatic stem cell population maintenance ... ventral midline determination / mesenchymal to epithelial transition involved in metanephric renal vesicle formation / response to inositol / regulation of heart morphogenesis / contact inhibition / negative regulation of hair follicle development / central nervous system neuron differentiation / 9+0 non-motile cilium / pancreas morphogenesis / regulation of somatic stem cell population maintenance / epithelial-mesenchymal cell signaling / myoblast migration / atrial septum morphogenesis / spinal cord dorsal/ventral patterning / determination of left/right asymmetry in lateral mesoderm / left/right axis specification / ciliary tip / Activation of SMO / patched binding / forebrain morphogenesis / type B pancreatic cell development / somite development / positive regulation of organ growth / dorsal/ventral neural tube patterning / BBSome-mediated cargo-targeting to cilium / smooth muscle tissue development / cellular response to cholesterol / thalamus development / positive regulation of branching involved in ureteric bud morphogenesis / cerebellar cortex morphogenesis / mammary gland epithelial cell differentiation / dentate gyrus development / pattern specification process / commissural neuron axon guidance / dopaminergic neuron differentiation / oxysterol binding / positive regulation of multicellular organism growth / positive regulation of smoothened signaling pathway / Class B/2 (Secretin family receptors) / neural crest cell migration / cAMP-dependent protein kinase inhibitor activity / cell fate specification / negative regulation of DNA binding / anterior/posterior pattern specification / positive regulation of mesenchymal cell proliferation / ciliary membrane / midgut development / hair follicle morphogenesis / smoothened signaling pathway / negative regulation of epithelial cell differentiation / positive regulation of neuroblast proliferation / protein kinase A catalytic subunit binding / heart looping / endoplasmic reticulum-Golgi intermediate compartment / odontogenesis of dentin-containing tooth / neuroblast proliferation / vasculogenesis / Hedgehog 'off' state / negative regulation of protein phosphorylation / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / T cell migration / D2 dopamine receptor binding / skeletal muscle fiber development / response to prostaglandin E / G protein-coupled serotonin receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / adenylate cyclase regulator activity / homeostasis of number of cells within a tissue / regulation of mitotic spindle organization / centriole / protein sequestering activity / cellular response to forskolin / positive regulation of epithelial cell proliferation / epithelial cell proliferation / central nervous system development / astrocyte activation / Regulation of insulin secretion / G protein-coupled receptor binding / positive regulation of cholesterol biosynthetic process / Hedgehog 'on' state / G protein-coupled receptor activity / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / multicellular organism growth / cerebral cortex development / cilium / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / response to peptide hormone / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / positive regulation of protein import into nucleus / Prostacyclin signalling through prostacyclin receptor 類似検索 - 分子機能 Smoothened, transmembrane domain / Smoothened, cysteine-rich domain / Frizzled/Smoothened, transmembrane domain / Frizzled/Smoothened family membrane region / Frizzled/Smoothened family membrane region / Frizzled/secreted frizzled-related protein / Frizzled / Frizzled domain / Frizzled cysteine-rich domain superfamily / Fz domain ... Smoothened, transmembrane domain / Smoothened, cysteine-rich domain / Frizzled/Smoothened, transmembrane domain / Frizzled/Smoothened family membrane region / Frizzled/Smoothened family membrane region / Frizzled/secreted frizzled-related protein / Frizzled / Frizzled domain / Frizzled cysteine-rich domain superfamily / Fz domain / Frizzled (fz) domain profile. / GPCR, family 2-like / G-protein coupled receptors family 2 profile 2. / 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 / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / 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 / Protein smoothened 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 / 解像度 : 3.84 Å 詳細 データ登録者Qi X / Li X 引用ジャーナル : Nature / 年 : 2019タイトル : Cryo-EM structure of oxysterol-bound human Smoothened coupled to a heterotrimeric G.著者 : Xiaofeng Qi / Heng Liu / Bonne Thompson / Jeffrey McDonald / Cheng Zhang / Xiaochun Li / 要旨 : The oncoprotein Smoothened (SMO), a G-protein-coupled receptor (GPCR) of the Frizzled-class (class-F), transduces the Hedgehog signal from the tumour suppressor Patched-1 (PTCH1) to the glioma- ... The oncoprotein Smoothened (SMO), a G-protein-coupled receptor (GPCR) of the Frizzled-class (class-F), transduces the Hedgehog signal from the tumour suppressor Patched-1 (PTCH1) to the glioma-associated-oncogene (GLI) transcription factors, which activates the Hedgehog signalling pathway. It has remained unknown how PTCH1 modulates SMO, how SMO is stimulated to form a complex with heterotrimeric G proteins and whether G-protein coupling contributes to the activation of GLI proteins. Here we show that 24,25-epoxycholesterol, which we identify as an endogenous ligand of PTCH1, can stimulate Hedgehog signalling in cells and can trigger G-protein signalling via human SMO in vitro. We present a cryo-electron microscopy structure of human SMO bound to 24(S),25-epoxycholesterol and coupled to a heterotrimeric G protein. The structure reveals a ligand-binding site for 24(S),25-epoxycholesterol in the 7-transmembrane region, as well as a G-coupled activation mechanism of human SMO. Notably, the G protein presents a different arrangement from that of class-A GPCR-G complexes. Our work provides molecular insights into Hedgehog signal transduction and the activation of a class-F GPCR. 履歴 登録 2019年5月2日 - ヘッダ(付随情報) 公開 2019年6月12日 - マップ公開 2019年6月12日 - 更新 2024年11月13日 - 現状 2024年11月13日 処理サイト : RCSB / 状態 : 公開
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