登録情報 データベース : EMDB / ID : EMD-13386 構造の表示 ダウンロードとリンクタイトル Low resolution Cryo-EM structure of full-length insulin receptor bound to 3 insulin, conf 1 マップデータ 詳細 試料複合体 : DDM solubilised full-length human insulin receptor with three insulins boundタンパク質・ペプチド : Isoform Short of Insulin receptorタンパク質・ペプチド : Insulinタンパク質・ペプチド : Insulin 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
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 / PTB domain binding / negative regulation of NAD(P)H oxidase activity / negative regulation of glycogen catabolic process / regulation of cellular amino acid metabolic process / adrenal gland development / positive regulation of nitric oxide mediated signal transduction / negative regulation of fatty acid metabolic process / neuronal cell body membrane / negative regulation of feeding behavior / Signaling by Insulin receptor / IRS activation / activation of protein kinase activity / Insulin processing / regulation of protein secretion / amyloid-beta clearance / positive regulation of respiratory burst / positive regulation of peptide hormone secretion / Regulation of gene expression in beta cells / negative regulation of acute inflammatory response / positive regulation of receptor internalization / alpha-beta T cell activation / regulation of embryonic development / negative regulation of respiratory burst involved in inflammatory response / transport across blood-brain barrier / insulin receptor substrate binding / positive regulation of dendritic spine maintenance / positive regulation of glycogen biosynthetic process / Synthesis, secretion, and deacylation of Ghrelin / epidermis development / negative regulation of protein secretion / regulation of protein localization to plasma membrane / fatty acid homeostasis / Signal attenuation / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / negative regulation of lipid catabolic process / negative regulation of gluconeogenesis / phosphatidylinositol 3-kinase binding / COPI-mediated anterograde transport / positive regulation of lipid biosynthetic process / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / heart morphogenesis / negative regulation of reactive oxygen species biosynthetic process / positive regulation of insulin receptor signaling pathway / nitric oxide-cGMP-mediated signaling / transport vesicle / positive regulation of protein autophosphorylation / dendrite membrane / Insulin receptor recycling / neuron projection maintenance / NPAS4 regulates expression of target genes / positive regulation of protein metabolic process / positive regulation of brown fat cell differentiation / positive regulation of glycolytic process / activation of protein kinase B activity / endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of mitotic nuclear division / Insulin receptor signalling cascade / receptor-mediated endocytosis / learning / positive regulation of nitric-oxide synthase activity / positive regulation of cytokine production / positive regulation of long-term synaptic potentiation / caveola / Regulation of insulin secretion / acute-phase response / endosome lumen / positive regulation of protein secretion / positive regulation of glucose import / positive regulation of cell differentiation / negative regulation of proteolysis / regulation of transmembrane transporter activity / insulin-like growth factor receptor binding / positive regulation of MAP kinase activity / wound healing / insulin receptor binding / regulation of synaptic plasticity / negative regulation of protein catabolic process / hormone activity / receptor internalization / receptor protein-tyrosine kinase / memory / cellular response to growth factor stimulus / cognition / positive regulation of neuron projection development / 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, conserved site / Insulin family signature. ... 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, 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 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 / 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・相同性生物種 Homo sapiens (ヒト)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 6.7 Å 詳細 データ登録者Nielsen JA / Slaaby R / Boesen T / Hummelshoj T / Brandt J / Schluckebier G / Nissen P 資金援助 デンマーク, 1件 詳細 詳細を隠すOrganization Grant number 国 Other government デンマーク
引用ジャーナル : J Mol Biol / 年 : 2022タイトル : Structural Investigations of Full-Length Insulin Receptor Dynamics and Signalling.著者 : Jeppe Nielsen / Jakob Brandt / Thomas Boesen / Tina Hummelshøj / Rita Slaaby / Gerd Schluckebier / Poul Nissen / 要旨 : Insulin regulates glucose homeostasis via binding and activation of the insulin receptor dimer at two distinct pairs of binding sites 1 and 2. Here, we present cryo-EM studies of full-length human ... Insulin regulates glucose homeostasis via binding and activation of the insulin receptor dimer at two distinct pairs of binding sites 1 and 2. Here, we present cryo-EM studies of full-length human insulin receptor (hIR) in an active state obtained at non-saturating, physiologically relevant insulin conditions. Insulin binds asymmetrically to the receptor under these conditions, occupying up to three of the four possible binding sites. Deletion analysis of the receptor together with site specific peptides and insulin analogs used in binding studies show that both sites 1 and 2 are required for high insulin affinity. We identify a homotypic interaction of the fibronectin type III domain (FnIII-3) of IR resulting in tight interaction of membrane proximal domains of the active, asymmetric receptor dimer. Our results show how insulin binding at two distinct types of sites disrupts the autoinhibited apo-IR dimer and stabilizes the active dimer. We propose an insulin binding and activation mechanism, which is sequential, exhibits negative cooperativity, and is based on asymmetry at physiological insulin concentrations with one to three insulin molecules activating IR. 履歴 登録 2021年8月12日 - ヘッダ(付随情報) 公開 2022年2月2日 - マップ公開 2022年2月2日 - 更新 2022年2月16日 - 現状 2022年2月16日 処理サイト : PDBe / 状態 : 公開
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