+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-20190 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
タイトル | Structure of human Smoothened-Gi complex | |||||||||
マップデータ | Smoothened-Gi complex | |||||||||
試料 |
| |||||||||
キーワード | GPCR / Complex / Hedgehog signaling / SIGNALING PROTEIN | |||||||||
機能・相同性 | 機能・相同性情報 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 / spinal cord dorsal/ventral patterning / determination of left/right asymmetry in lateral mesoderm / left/right axis specification / Activation of SMO / ciliary tip / patched binding / somite development / forebrain morphogenesis / type B pancreatic cell development / thalamus development / positive regulation of organ growth / positive regulation of branching involved in ureteric bud morphogenesis / cellular response to cholesterol / dorsal/ventral neural tube patterning / smooth muscle tissue development / BBSome-mediated cargo-targeting to cilium / 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 / anterior/posterior pattern specification / positive regulation of mesenchymal cell proliferation / ciliary membrane / midgut development / negative regulation of epithelial cell differentiation / hair follicle morphogenesis / smoothened signaling pathway / positive regulation of neuroblast proliferation / heart looping / negative regulation of DNA binding / protein kinase A catalytic subunit binding / odontogenesis of dentin-containing tooth / endoplasmic reticulum-Golgi intermediate compartment / neuroblast proliferation / T cell migration / vasculogenesis / Hedgehog 'off' state / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / skeletal muscle fiber development / G protein-coupled serotonin receptor binding / homeostasis of number of cells within a tissue / regulation of mitotic spindle organization / cellular response to forskolin / protein sequestering activity / centriole / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / positive regulation of epithelial cell proliferation / epithelial cell proliferation / negative regulation of protein phosphorylation / central nervous system development / Regulation of insulin secretion / astrocyte activation / G protein-coupled receptor binding / G protein-coupled receptor activity / Hedgehog 'on' state / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / multicellular organism growth / 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 / cilium / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / cerebral cortex development / 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 / response to peptide hormone / G beta:gamma signalling through CDC42 / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste 類似検索 - 分子機能 | |||||||||
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 | |||||||||
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 |
|
-構造の表示
ムービー |
ムービービューア |
---|---|
構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_20190.map.gz | 78.3 MB | EMDBマップデータ形式 | |
---|---|---|---|---|
ヘッダ (付随情報) | emd-20190-v30.xml emd-20190.xml | 18.1 KB 18.1 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_20190.png | 58.4 KB | ||
Filedesc metadata | emd-20190.cif.gz | 6.4 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-20190 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20190 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_20190_validation.pdf.gz | 586.6 KB | 表示 | EMDB検証レポート |
---|---|---|---|---|
文書・詳細版 | emd_20190_full_validation.pdf.gz | 586.2 KB | 表示 | |
XML形式データ | emd_20190_validation.xml.gz | 6.3 KB | 表示 | |
CIF形式データ | emd_20190_validation.cif.gz | 7.3 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20190 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20190 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
---|---|
「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_20190.map.gz / 形式: CCP4 / 大きさ: 83.7 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | Smoothened-Gi complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.07 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
|
-添付データ
-試料の構成要素
+全体 : Smoothened-Gi-Fab complex
+超分子 #1: Smoothened-Gi-Fab complex
+超分子 #2: Smoothened homolog
+超分子 #3: Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine ...
+超分子 #4: Fab light chain, Fab heavy chain
+分子 #1: Smoothened homolog
+分子 #2: Guanine nucleotide-binding protein G(i) subunit alpha-1
+分子 #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+分子 #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+分子 #5: Fab light chain
+分子 #6: Fab heavy chain
+分子 #7: 17-[3-(3,3-DIMETHYL-OXIRANYL)-1-METHYL-PROPYL]-10,13-DIMETHYL-2,3...
-実験情報
-構造解析
解析 | 単粒子再構成法 |
---|---|
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 7.5 |
---|
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
---|---|
撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 平均電子線量: 1.4 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: DARK FIELD |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |