登録情報 データベース : PDB / ID : 7sti 構造の表示 ダウンロードとリンクタイトル Full-length insulin receptor bound with unsaturated insulin WT (1 insulin bound) asymmetric conformation 要素Insulin receptor インスリン受容体 Insulin インスリン 詳細キーワード SIGNALING PROTEIN / insulin receptor (インスリン受容体) / site 1 binding deficient mutant insulin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 Insulin receptor / Insulin receptor recycling / 卵黄 / IRS activation / Insulin receptor signalling cascade / Signal attenuation / 3-phosphoinositide-dependent protein kinase binding / positive regulation of glycoprotein biosynthetic process / lipoic acid binding / regulation of hydrogen peroxide metabolic process ... Signaling by Insulin receptor / Insulin receptor recycling / 卵黄 / IRS activation / Insulin receptor signalling cascade / Signal attenuation / 3-phosphoinositide-dependent protein kinase binding / positive regulation of glycoprotein biosynthetic process / lipoic acid binding / regulation of hydrogen peroxide metabolic process / regulation of female gonad development / positive regulation of meiotic cell cycle / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / positive regulation of developmental growth / insulin-like growth factor II binding / nuclear lumen / 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 / negative regulation of fatty acid metabolic process / neuronal cell body membrane / negative regulation of feeding behavior / Signaling by Insulin receptor / nitric oxide-cGMP-mediated signaling / IRS activation / Insulin processing / regulation of protein secretion / amyloid-beta clearance / positive regulation of peptide hormone secretion / positive regulation of respiratory burst / Regulation of gene expression in beta cells / negative regulation of acute inflammatory response / regulation of embryonic development / positive regulation of receptor internalization / alpha-beta T cell activation / 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 / Synthesis, secretion, and deacylation of Ghrelin / epidermis development / negative regulation of protein secretion / positive regulation of nitric oxide mediated signal transduction / fatty acid homeostasis / regulation of protein localization to plasma membrane / Signal attenuation / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / response to tumor necrosis factor / negative regulation of lipid catabolic process / negative regulation of gluconeogenesis / phosphatidylinositol 3-kinase binding / COPI-mediated anterograde transport / positive regulation of lipid biosynthetic process / heart morphogenesis / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / negative regulation of reactive oxygen species biosynthetic process / positive regulation of insulin receptor signaling pathway / positive regulation of phosphorylation / 小胞 / positive regulation of protein autophosphorylation / dendrite membrane / Insulin receptor recycling / insulin-like growth factor receptor binding / neuron projection maintenance / NPAS4 regulates expression of target genes / positive regulation of protein metabolic process / positive regulation of brown fat cell differentiation / endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of glycolytic process / activation of protein kinase B activity / positive regulation of mitotic nuclear division / receptor-mediated endocytosis / Insulin receptor signalling cascade / response to nutrient levels / negative regulation of protein phosphorylation / positive regulation of cytokine production / positive regulation of long-term synaptic potentiation / Regulation of insulin secretion / カベオラ / acute-phase response / endosome lumen / positive regulation of protein secretion / positive regulation of glucose import / positive regulation of nitric-oxide synthase activity / positive regulation of cell differentiation / negative regulation of proteolysis / regulation of transmembrane transporter activity / animal organ morphogenesis / wound healing 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. / インスリン / 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. / インスリン / 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 / フィブロネクチンIII型ドメイン / 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 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 : 4.9 Å 詳細データ登録者 Bai, X.C. / Choi, E. 資金援助 米国, 1件 詳細 詳細を隠す組織 認可番号 国 National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) R01GM136976 米国
引用ジャーナル : Nat Struct Mol Biol / 年 : 2022タイトル : Synergistic activation of the insulin receptor via two distinct sites.著者 : Jie Li / Junhee Park / John P Mayer / Kristofor J Webb / Emiko Uchikawa / Jiayi Wu / Shun Liu / Xuewu Zhang / Michael H B Stowell / Eunhee Choi / Xiao-Chen Bai / 要旨 : Insulin receptor (IR) signaling controls multiple facets of animal physiology. Maximally four insulins bind to IR at two distinct sites, termed site-1 and site-2. However, the precise functional ... Insulin receptor (IR) signaling controls multiple facets of animal physiology. Maximally four insulins bind to IR at two distinct sites, termed site-1 and site-2. However, the precise functional roles of each binding event during IR activation remain unresolved. Here, we showed that IR incompletely saturated with insulin predominantly forms an asymmetric conformation and exhibits partial activation. IR with one insulin bound adopts a Γ-shaped conformation. IR with two insulins bound assumes a Ƭ-shaped conformation. One insulin binds at site-1 and another simultaneously contacts both site-1 and site-2 in the Ƭ-shaped IR dimer. We further show that concurrent binding of four insulins to sites-1 and -2 prevents the formation of asymmetric IR and promotes the T-shaped symmetric, fully active state. Collectively, our results demonstrate how the synergistic binding of multiple insulins promotes optimal IR activation. 履歴 登録 2021年11月13日 登録サイト : RCSB / 処理サイト : RCSB改定 1.0 2022年3月30日 Provider : repository / タイプ : Initial release改定 1.1 2022年4月13日 Group : Database references / カテゴリ : citation / citation_authorItem : _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title改定 1.2 2022年4月27日 Group : Database references / カテゴリ : citation / citation_authorItem : _citation.journal_volume / _citation.page_first ... _citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
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