登録情報 データベース : EMDB / ID : EMD-22119 構造の表示 ダウンロードとリンクタイトル Structure of human SMO-Gi complex with SAG マップデータStructure of human SMO-Gi complex 詳細 試料複合体 : hSMO-Gi-SAG複合体 : hSMO複合体 : Gi複合体 : scFv16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 : Smoothened homologリガンド : 3-chloro-N-[trans-4-(methylamino)cyclohexyl]-N-{[3-(pyridin-4-yl)phenyl]methyl}-1-benzothiophene-2-carboxamide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
ventral midline determination / mesenchymal to epithelial transition involved in metanephric renal vesicle formation / 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 ... ventral midline determination / mesenchymal to epithelial transition involved in metanephric renal vesicle formation / 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 / determination of left/right asymmetry in lateral mesoderm / spinal cord dorsal/ventral patterning / left/right axis specification / ciliary tip / Activation of SMO / thalamus development / somite development / patched binding / forebrain morphogenesis / cellular response to cholesterol / type B pancreatic cell development / positive regulation of branching involved in ureteric bud morphogenesis / positive regulation of organ growth / BBSome-mediated cargo-targeting to cilium / dorsal/ventral neural tube patterning / smooth muscle tissue development / pattern specification process / cerebellar cortex morphogenesis / mammary gland epithelial cell differentiation / dentate gyrus development / dopaminergic neuron differentiation / commissural neuron axon guidance / oxysterol binding / positive regulation of multicellular organism growth / positive regulation of smoothened signaling pathway / Class B/2 (Secretin family receptors) / neural crest cell migration / cell fate specification / cAMP-dependent protein kinase inhibitor activity / ciliary membrane / anterior/posterior pattern specification / positive regulation of mesenchymal cell proliferation / negative regulation of epithelial cell differentiation / midgut development / hair follicle morphogenesis / smoothened signaling pathway / positive regulation of neuroblast proliferation / heart looping / negative regulation of DNA binding / odontogenesis of dentin-containing tooth / protein kinase A catalytic subunit binding / endoplasmic reticulum-Golgi intermediate compartment / neuroblast proliferation / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / vasculogenesis / regulation of cAMP-mediated signaling / Hedgehog 'off' state / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / skeletal muscle fiber development / regulation of mitotic spindle organization / homeostasis of number of cells within a tissue / cellular response to forskolin / protein sequestering activity / centriole / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / positive regulation of epithelial cell proliferation / negative regulation of protein phosphorylation / epithelial cell proliferation / central nervous system development / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / astrocyte activation / Hedgehog 'on' state / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / multicellular organism growth / 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 / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / cilium / cerebral cortex development / response to peptide hormone / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste 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 / 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 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 / クライオ電子顕微鏡法 / 解像度 : 3.96 Å 詳細 データ登録者Qi X / Li X 引用ジャーナル : Nat Chem Biol / 年 : 2020タイトル : Sterols in an intramolecular channel of Smoothened mediate Hedgehog signaling.著者 : Xiaofeng Qi / Lucas Friedberg / Ryan De Bose-Boyd / Tao Long / Xiaochun Li / 要旨 : Smoothened (SMO), a class Frizzled G protein-coupled receptor (class F GPCR), transduces the Hedgehog signal across the cell membrane. Sterols can bind to its extracellular cysteine-rich domain ... Smoothened (SMO), a class Frizzled G protein-coupled receptor (class F GPCR), transduces the Hedgehog signal across the cell membrane. Sterols can bind to its extracellular cysteine-rich domain (CRD) and to several sites in the seven transmembrane helices (7-TMs) of SMO. However, the mechanism by which sterols regulate SMO via multiple sites is unknown. Here we determined the structures of SMO-G complexes bound to the synthetic SMO agonist (SAG) and to 24(S),25-epoxycholesterol (24(S),25-EC). A novel sterol-binding site in the extracellular extension of TM6 was revealed to connect other sites in 7-TMs and CRD, forming an intramolecular sterol channel from the middle side of 7-TMs to CRD. Additional structures of two gain-of-function variants, SMO and SMO, showed that blocking the channel at its midpoints allows sterols to occupy the binding sites in 7-TMs, thereby activating SMO. These data indicate that sterol transport through the core of SMO is a major regulator of SMO-mediated signaling. 履歴 登録 2020年6月6日 - ヘッダ(付随情報) 公開 2020年9月30日 - マップ公開 2020年9月30日 - 更新 2020年11月25日 - 現状 2020年11月25日 処理サイト : RCSB / 状態 : 公開
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