登録情報 データベース : EMDB / ID : EMD-34018 ダウンロードとリンクタイトル human insulin receptor bound with A43 DNA aptamer and insulin マップデータ 詳細 試料複合体 : receptor-ligand complex複合体 : Insulin, Insulin receptorタンパク質・ペプチド : Insulin A chainタンパク質・ペプチド : Insulin, isoform 2タンパク質・ペプチド : Isoform Short of Insulin receptor複合体 : DNA 28mer 詳細 キーワード receptor-ligand complex / STRUCTURAL 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
regulation of female gonad development / positive regulation of meiotic cell cycle / positive regulation of developmental growth / insulin-like growth factor II binding / male sex determination / exocrine pancreas development / insulin receptor complex / insulin-like growth factor I binding / insulin receptor activity / positive regulation of protein-containing complex disassembly ... regulation of female gonad development / positive regulation of meiotic cell cycle / positive regulation of developmental growth / insulin-like growth factor II binding / male sex determination / exocrine pancreas development / insulin receptor complex / insulin-like growth factor I binding / insulin receptor activity / positive regulation of protein-containing complex disassembly / cargo receptor activity / dendritic spine maintenance / insulin binding / negative regulation of NAD(P)H oxidase activity / negative regulation of glycogen catabolic process / PTB domain binding / adrenal gland development / positive regulation of nitric oxide mediated signal transduction / negative regulation of fatty acid metabolic process / negative regulation of feeding behavior / Signaling by Insulin receptor / activation of protein kinase activity / IRS activation / Insulin processing / neuronal cell body membrane / regulation of protein secretion / positive regulation of peptide hormone secretion / positive regulation of respiratory burst / negative regulation of acute inflammatory response / Regulation of gene expression in beta cells / positive regulation of receptor internalization / amyloid-beta clearance / alpha-beta T cell activation / transport across blood-brain barrier / regulation of embryonic development / regulation of amino acid metabolic process / negative regulation of respiratory burst involved in inflammatory response / insulin receptor substrate binding / positive regulation of dendritic spine maintenance / positive regulation of glycogen biosynthetic process / epidermis development / Synthesis, secretion, and deacylation of Ghrelin / negative regulation of protein secretion / regulation of protein localization to plasma membrane / fatty acid homeostasis / negative regulation of gluconeogenesis / Signal attenuation / negative regulation of lipid catabolic process / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / COPI-mediated anterograde transport / phosphatidylinositol 3-kinase binding / heart morphogenesis / positive regulation of lipid biosynthetic process / positive regulation of insulin receptor signaling pathway / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / negative regulation of reactive oxygen species biosynthetic process / nitric oxide-cGMP-mediated signaling / positive regulation of protein autophosphorylation / transport vesicle / insulin-like growth factor receptor binding / Insulin receptor recycling / dendrite membrane / neuron projection maintenance / NPAS4 regulates expression of target genes / positive regulation of protein metabolic process / positive regulation of brown fat cell differentiation / activation of protein kinase B activity / endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of glycolytic process / Insulin receptor signalling cascade / positive regulation of mitotic nuclear division / receptor-mediated endocytosis / positive regulation of nitric-oxide synthase activity / learning / acute-phase response / positive regulation of cytokine production / cognition / positive regulation of long-term synaptic potentiation / Regulation of insulin secretion / endosome lumen / positive regulation of D-glucose import / positive regulation of protein secretion / negative regulation of proteolysis / positive regulation of cell differentiation / regulation of transmembrane transporter activity / insulin receptor binding / wound healing / positive regulation of MAP kinase activity / negative regulation of protein catabolic process / receptor protein-tyrosine kinase / hormone activity / caveola / regulation of synaptic plasticity / receptor internalization / cellular response to growth factor stimulus / positive regulation of neuron projection development / memory / positive regulation of protein localization to nucleus / Golgi lumen / peptidyl-tyrosine phosphorylation 類似検索 - 分子機能 Insulin receptor, trans-membrane domain / Insulin receptor trans-membrane segment / Tyrosine-protein kinase, insulin-like receptor / Tyrosine-protein kinase, receptor class II, conserved site / Receptor tyrosine kinase class II signature. / Insulin / Insulin family / Insulin/IGF/Relaxin family / Insulin-like / Insulin / insulin-like growth factor / relaxin family. ... Insulin receptor, trans-membrane domain / Insulin receptor trans-membrane segment / Tyrosine-protein kinase, insulin-like receptor / Tyrosine-protein kinase, receptor class II, conserved site / Receptor tyrosine kinase class II signature. / Insulin / Insulin family / Insulin/IGF/Relaxin family / Insulin-like / Insulin / insulin-like growth factor / relaxin family. / Insulin, conserved site / Insulin family signature. / 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 III domain / 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 / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / 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, isoform 2 / Insulin / Insulin receptor 類似検索 - 構成要素生物種 Homo sapiens (ヒト) / synthetic construct (人工物) 手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.6 Å 詳細 データ登録者Kim J / Yunn N / Ryu S / Cho Y 資金援助 韓国, 1件 詳細 詳細を隠すOrganization Grant number 国 National Research Foundation (NRF, Korea) 2017M3A9F6029736 韓国
引用ジャーナル : Nat Commun / 年 : 2022タイトル : Functional selectivity of insulin receptor revealed by aptamer-trapped receptor structures.著者 : Junhong Kim / Na-Oh Yunn / Mangeun Park / Jihan Kim / Seongeun Park / Yoojoong Kim / Jeongeun Noh / Sung Ho Ryu / Yunje Cho / 要旨 : Activation of insulin receptor (IR) initiates a cascade of conformational changes and autophosphorylation events. Herein, we determined three structures of IR trapped by aptamers using cryo-electron ... Activation of insulin receptor (IR) initiates a cascade of conformational changes and autophosphorylation events. Herein, we determined three structures of IR trapped by aptamers using cryo-electron microscopy. The A62 agonist aptamer selectively activates metabolic signaling. In the absence of insulin, the two A62 aptamer agonists of IR adopt an insulin-accessible arrowhead conformation by mimicking site-1/site-2' insulin coordination. Insulin binding at one site triggers conformational changes in one protomer, but this movement is blocked in the other protomer by A62 at the opposite site. A62 binding captures two unique conformations of IR with a similar stalk arrangement, which underlie Tyr1150 mono-phosphorylation (m-pY1150) and selective activation for metabolic signaling. The A43 aptamer, a positive allosteric modulator, binds at the opposite side of the insulin-binding module, and stabilizes the single insulin-bound IR structure that brings two FnIII-3 regions into closer proximity for full activation. Our results suggest that spatial proximity of the two FnIII-3 ends is important for m-pY1150, but multi-phosphorylation of IR requires additional conformational rearrangement of intracellular domains mediated by coordination between extracellular and transmembrane domains. 履歴 登録 2022年8月5日 - ヘッダ(付随情報) 公開 2022年11月9日 - マップ公開 2022年11月9日 - 更新 2024年5月8日 - 現状 2024年5月8日 処理サイト : PDBj / 状態 : 公開
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