登録情報 データベース : PDB / ID : 6pyh 構造の表示 ダウンロードとリンクタイトル Cryo-EM structure of full-length IGF1R-IGF1 complex. Only the extracellular region of the complex is resolved. 要素Insulin-like growth factor 1 receptor Insulin-like growth factor I 詳細キーワード SIGNALING PROTEIN/HORMONE / IGF1R / IGF1 / SIGNALING PROTEIN-HORMONE complex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
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / mitotic nuclear division / IRS-related events triggered by IGF1R / SHC-related events triggered by IGF1R / glycolate metabolic process / muscle hypertrophy / negative regulation of oocyte development / positive regulation of trophectodermal cell proliferation / insulin-like growth factor binding protein complex / insulin-like growth factor ternary complex ... Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / mitotic nuclear division / IRS-related events triggered by IGF1R / SHC-related events triggered by IGF1R / glycolate metabolic process / muscle hypertrophy / negative regulation of oocyte development / positive regulation of trophectodermal cell proliferation / insulin-like growth factor binding protein complex / insulin-like growth factor ternary complex / : / proteoglycan biosynthetic process / negative regulation of cholangiocyte apoptotic process / positive regulation of glycoprotein biosynthetic process / myotube cell development / Extra-nuclear estrogen signaling / skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration / insulin-like growth factor receptor activity / positive regulation of steroid hormone biosynthetic process / negative regulation of neuroinflammatory response / protein kinase complex / bone mineralization involved in bone maturation / Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / positive regulation of cell growth involved in cardiac muscle cell development / negative regulation of vascular associated smooth muscle cell apoptotic process / protein transporter activity / IRS-related events triggered by IGF1R / insulin-like growth factor binding / exocytic vesicle / negative regulation of muscle cell apoptotic process / positive regulation of meiotic cell cycle / positive regulation of DNA metabolic process / positive regulation of developmental growth / cell activation / positive regulation of calcineurin-NFAT signaling cascade / male sex determination / prostate gland epithelium morphogenesis / exocrine pancreas development / mammary gland development / insulin receptor complex / negative regulation of hepatocyte apoptotic process / positive regulation of transcription regulatory region DNA binding / insulin-like growth factor I binding / insulin receptor activity / transcytosis / alphav-beta3 integrin-IGF-1-IGF1R complex / positive regulation of kinase activity / positive regulation of Ras protein signal transduction / positive regulation of protein-containing complex disassembly / myoblast differentiation / positive regulation of insulin-like growth factor receptor signaling pathway / myoblast proliferation / muscle organ development / negative regulation of interleukin-1 beta production / dendritic spine maintenance / cellular response to insulin-like growth factor stimulus / response to L-glutamate / insulin binding / negative regulation of MAPK cascade / adrenal gland development / establishment of cell polarity / postsynaptic modulation of chemical synaptic transmission / protein tyrosine kinase activator activity / positive regulation of cardiac muscle hypertrophy / positive regulation of activated T cell proliferation / positive regulation of smooth muscle cell migration / positive regulation of axon regeneration / amyloid-beta clearance / negative regulation of release of cytochrome c from mitochondria / positive regulation of osteoblast proliferation / positive regulation of cytokinesis / negative regulation of amyloid-beta formation / negative regulation of smooth muscle cell apoptotic process / phosphatidylinositol-mediated signaling / regulation of JNK cascade / negative regulation of tumor necrosis factor production / insulin receptor substrate binding / estrous cycle / positive regulation of glycogen biosynthetic process / G-protein alpha-subunit binding / Synthesis, secretion, and deacylation of Ghrelin / epidermis development / epithelial to mesenchymal transition / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of DNA binding / SHC-related events triggered by IGF1R / positive regulation of osteoblast differentiation / phosphatidylinositol 3-kinase binding / peptidyl-tyrosine autophosphorylation / positive regulation of tyrosine phosphorylation of STAT protein / positive regulation of vascular associated smooth muscle cell proliferation / cellular response to transforming growth factor beta stimulus / cell surface receptor protein tyrosine kinase signaling pathway / T-tubule / positive regulation of glycolytic process / activation of protein kinase B activity / transmembrane receptor protein tyrosine kinase activity / protein serine/threonine kinase activator activity / positive regulation of mitotic nuclear division / cerebellum development 類似検索 - 分子機能 Insulin-like growth factor I / Insulin-like growth factor / Tyrosine-protein kinase, insulin-like receptor / Tyrosine-protein kinase, receptor class II, conserved site / Receptor tyrosine kinase class II signature. / Insulin family / Insulin/IGF/Relaxin family / Insulin, conserved site / Insulin family signature. / Insulin-like ... Insulin-like growth factor I / Insulin-like growth factor / Tyrosine-protein kinase, insulin-like receptor / Tyrosine-protein kinase, receptor class II, conserved site / Receptor tyrosine kinase class II signature. / Insulin family / Insulin/IGF/Relaxin family / Insulin, conserved site / Insulin family signature. / Insulin-like / Insulin / insulin-like growth factor / relaxin family. / Insulin-like superfamily / Receptor L-domain / Furin-like cysteine-rich domain / Receptor L-domain superfamily / Furin-like cysteine rich region / Receptor L domain / Furin-like repeat / Furin-like repeats / Growth factor receptor cysteine-rich domain superfamily / Fibronectin type 3 domain / Fibronectin type-III domain profile. / Fibronectin type III / Fibronectin type III superfamily / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Immunoglobulin-like fold / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily 類似検索 - ドメイン・相同性 Insulin-like growth factor I / Insulin-like growth factor 1 receptor 類似検索 - 構成要素生物種 Mus musculus (ハツカネズミ)Homo sapiens (ヒト)手法 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 4.3 Å 詳細データ登録者 Li, J. / Choi, E. / Yu, H.T. / Bai, X.C. 引用ジャーナル : Nat Commun / 年 : 2019タイトル : Structural basis of the activation of type 1 insulin-like growth factor receptor.著者 : Jie Li / Eunhee Choi / Hongtao Yu / Xiao-Chen Bai / 要旨 : Type 1 insulin-like growth factor receptor (IGF1R) is a receptor tyrosine kinase that regulates cell growth and proliferation, and can be activated by IGF1, IGF2, and insulin. Here, we report the ... Type 1 insulin-like growth factor receptor (IGF1R) is a receptor tyrosine kinase that regulates cell growth and proliferation, and can be activated by IGF1, IGF2, and insulin. Here, we report the cryo-EM structure of full-length IGF1R-IGF1 complex in the active state. This structure reveals that only one IGF1 molecule binds the Γ-shaped asymmetric IGF1R dimer. The IGF1-binding site is formed by the L1 and CR domains of one IGF1R protomer and the α-CT and FnIII-1 domains of the other. The liganded α-CT forms a rigid beam-like structure with the unliganded α-CT, which hinders the conformational change of the unliganded α-CT required for binding of a second IGF1 molecule. We further identify an L1-FnIII-2 interaction that mediates the dimerization of membrane-proximal domains of IGF1R. This interaction is required for optimal receptor activation. Our study identifies a source of the negative cooperativity in IGF1 binding to IGF1R and reveals the structural basis of IGF1R activation. 履歴 登録 2019年7月29日 登録サイト : RCSB / 処理サイト : RCSB改定 1.0 2019年10月23日 Provider : repository / タイプ : Initial release