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 キーワード GPCR / MEMBRANE 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 / 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 / response to inositol / regulation of heart morphogenesis / contact inhibition / negative regulation of hair follicle development / 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 / Activation of SMO / ciliary tip / 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 / cerebellar cortex morphogenesis / positive regulation of branching involved in ureteric bud morphogenesis / cellular response to cholesterol / pattern specification process / mammary gland epithelial cell differentiation / dentate gyrus development / central nervous system neuron differentiation / commissural neuron axon guidance / thalamus development / dopaminergic neuron differentiation / oxysterol binding / positive regulation of multicellular organism growth / positive regulation of smoothened signaling pathway / Class B/2 (Secretin family receptors) / cell fate specification / cAMP-dependent protein kinase inhibitor activity / neural crest cell migration / negative regulation of DNA binding / anterior/posterior pattern specification / positive regulation of mesenchymal cell proliferation / hair follicle morphogenesis / ciliary membrane / midgut development / smoothened signaling pathway / negative regulation of epithelial cell differentiation / positive regulation of neuroblast proliferation / heart looping / endoplasmic reticulum-Golgi intermediate compartment / protein kinase A catalytic subunit binding / odontogenesis of dentin-containing tooth / negative regulation of protein phosphorylation / neuroblast proliferation / adenylate cyclase inhibitor activity / vasculogenesis / Hedgehog 'off' state / positive regulation of protein localization to cell cortex / T cell migration / Adenylate cyclase inhibitory pathway / skeletal muscle fiber development / D2 dopamine receptor binding / response to prostaglandin E / G protein-coupled serotonin receptor binding / adenylate cyclase regulator activity / adenylate cyclase-inhibiting serotonin receptor signaling pathway / centriole / cellular response to forskolin / homeostasis of number of cells within a tissue / protein sequestering activity / regulation of mitotic spindle organization / positive regulation of epithelial cell proliferation / central nervous system development / epithelial cell proliferation / astrocyte activation / Regulation of insulin secretion / positive regulation of cholesterol biosynthetic process / negative regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / Hedgehog 'on' state / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / cerebral cortex development / response to peptide hormone / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / centriolar satellite / positive regulation of protein import into nucleus / multicellular organism growth / 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 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 / G protein beta WD-40 repeat protein / 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. / 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 2024年10月30日 - 現状 2024年10月30日 処理サイト : RCSB / 状態 : 公開
すべて表示 表示を減らす