登録情報 データベース : PDB / ID : 7sye 構造の表示 ダウンロードとリンクタイトル Cryo-EM structure of the extracellular module of the full-length EGFR bound to EGF. "tips-separated" conformation 要素Epidermal growth factor Epidermal growth factor receptor 詳細キーワード SIGNALING PROTEIN/RECEPTOR / receptor tyrosine kinases / epidermal growth factor receptor / SIGNALING PROTEIN / SIGNALING PROTEIN-RECEPTOR 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
positive regulation of hyaluronan biosynthetic process / negative regulation of secretion / negative regulation of cholesterol efflux / positive regulation of cerebellar granule cell precursor proliferation / positive regulation of epithelial tube formation / cerebellar granule cell precursor proliferation / positive regulation of protein localization to early endosome / regulation of protein localization to cell surface / regulation of calcium ion import / transmembrane receptor protein tyrosine kinase activator activity ... positive regulation of hyaluronan biosynthetic process / negative regulation of secretion / negative regulation of cholesterol efflux / positive regulation of cerebellar granule cell precursor proliferation / positive regulation of epithelial tube formation / cerebellar granule cell precursor proliferation / positive regulation of protein localization to early endosome / regulation of protein localization to cell surface / regulation of calcium ion import / transmembrane receptor protein tyrosine kinase activator activity / Developmental Lineage of Pancreatic Acinar Cells / positive regulation of ubiquitin-dependent protein catabolic process / Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin / positive regulation of protein kinase C activity / multivesicular body, internal vesicle lumen / negative regulation of cardiocyte differentiation / response to hydroxyisoflavone / diterpenoid metabolic process / positive regulation of prolactin secretion / Shc-EGFR complex / epidermal growth factor receptor binding / positive regulation of peptidyl-threonine phosphorylation / Inhibition of Signaling by Overexpressed EGFR / ovulation cycle / EGFR interacts with phospholipase C-gamma / regulation of receptor signaling pathway via JAK-STAT / positive regulation of mucus secretion / regulation of peptidyl-tyrosine phosphorylation / positive regulation of DNA binding / epidermal growth factor binding / NFE2L2 regulating tumorigenic genes / tongue development / response to UV-A / PLCG1 events in ERBB2 signaling / midgut development / ERBB2-EGFR signaling pathway / hydrogen peroxide metabolic process / morphogenesis of an epithelial fold / PTK6 promotes HIF1A stabilization / branching morphogenesis of an epithelial tube / ERBB2 Activates PTK6 Signaling / digestive tract morphogenesis / Signaling by EGFR / response to cobalamin / intracellular vesicle / eyelid development in camera-type eye / negative regulation of epidermal growth factor receptor signaling pathway / cerebral cortex cell migration / protein insertion into membrane / ERBB2 Regulates Cell Motility / hepatocyte growth factor receptor activity / platelet-derived growth factor beta-receptor activity / placental growth factor receptor activity / brain-derived neurotrophic factor receptor activity / boss receptor activity / platelet-derived growth factor alpha-receptor activity / epidermal growth factor receptor activity / macrophage colony-stimulating factor receptor activity / protein tyrosine kinase activator activity / protein tyrosine kinase collagen receptor activity / stem cell factor receptor activity / Respiratory syncytial virus (RSV) attachment and entry / positive regulation of bone resorption / positive regulation of receptor internalization / Signaling by ERBB4 / PI3K events in ERBB2 signaling / negative regulation of mitotic cell cycle / insulin-like growth factor receptor activity / transmembrane-ephrin receptor activity / positive regulation of phosphorylation / GPI-linked ephrin receptor activity / positive regulation of peptidyl-serine phosphorylation / mammary gland alveolus development / vascular endothelial growth factor receptor activity / peptidyl-tyrosine autophosphorylation / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / hair follicle development / MAP kinase kinase kinase activity / GAB1 signalosome / positive regulation of G1/S transition of mitotic cell cycle / fibroblast growth factor receptor activity / embryonic placenta development / insulin receptor activity / salivary gland morphogenesis / positive regulation of vasoconstriction / neuron projection morphogenesis / ERK1 and ERK2 cascade / Signaling by ERBB2 / positive regulation of endothelial cell proliferation / positive regulation of glial cell proliferation / GRB2 events in EGFR signaling / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / SHC1 events in EGFR signaling / transmembrane receptor protein tyrosine kinase activity / EGFR Transactivation by Gastrin / cellular response to dexamethasone stimulus / positive regulation of endothelial cell migration / GRB2 events in ERBB2 signaling / positive regulation of mitotic nuclear division / positive regulation of synaptic transmission, glutamatergic 類似検索 - 分子機能 Pro-epidermal growth factor / : / Low-density lipoprotein receptor repeat class B / LDL-receptor class B (LDLRB) repeat profile. / LDLR class B repeat / Low-density lipoprotein-receptor YWTD domain / : / Calcium-binding EGF domain / : / Epidermal growth factor receptor transmembrane-juxtamembrane segment ... Pro-epidermal growth factor / : / Low-density lipoprotein receptor repeat class B / LDL-receptor class B (LDLRB) repeat profile. / LDLR class B repeat / Low-density lipoprotein-receptor YWTD domain / : / Calcium-binding EGF domain / : / Epidermal growth factor receptor transmembrane-juxtamembrane segment / Tyrosine protein kinase, EGF/ERB/XmrK receptor / Growth factor receptor domain 4 / Growth factor receptor domain IV / Six-bladed beta-propeller, TolB-like / Coagulation Factor Xa inhibitory site / EGF-like domain / Receptor L-domain / Furin-like cysteine-rich domain / Receptor L-domain superfamily / Furin-like cysteine rich region / Receptor L domain / EGF-type aspartate/asparagine hydroxylation site / Furin-like repeat / Furin-like repeats / EGF-like calcium-binding, conserved site / Calcium-binding EGF-like domain signature. / Aspartic acid and asparagine hydroxylation site. / EGF-like calcium-binding domain / Calcium-binding EGF-like domain / Epidermal growth factor-like domain. / EGF-like domain profile. / Growth factor receptor cysteine-rich domain superfamily / EGF-like domain signature 1. / EGF-like domain signature 2. / : / EGF-like domain / 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. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily 類似検索 - ドメイン・相同性 Epidermal growth factor receptor / Pro-epidermal growth factor 類似検索 - 構成要素生物種 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 : 3.3 Å 詳細データ登録者 Huang, Y. / Ognjenovic, J. / Karandur, D. / Miller, K. / Merk, A. / Subramaniam, S. / Kuriyan, J. 資金援助 米国, 2件 詳細 詳細を隠す組織 認可番号 国 Canada Excellence Research Chair Award 米国 Howard Hughes Medical Institute (HHMI) 米国
引用ジャーナル : Elife / 年 : 2021タイトル : A molecular mechanism for the generation of ligand-dependent differential outputs by the epidermal growth factor receptor.著者 : Yongjian Huang / Jana Ognjenovic / Deepti Karandur / Kate Miller / Alan Merk / Sriram Subramaniam / John Kuriyan / 要旨 : The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that couples the binding of extracellular ligands, such as EGF and transforming growth factor-α (TGF-α), to the initiation ... The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that couples the binding of extracellular ligands, such as EGF and transforming growth factor-α (TGF-α), to the initiation of intracellular signaling pathways. EGFR binds to EGF and TGF-α with similar affinity, but generates different signals from these ligands. To address the mechanistic basis of this phenomenon, we have carried out cryo-EM analyses of human EGFR bound to EGF and TGF-α. We show that the extracellular module adopts an ensemble of dimeric conformations when bound to either EGF or TGF-α. The two extreme states of this ensemble represent distinct ligand-bound quaternary structures in which the membrane-proximal tips of the extracellular module are either juxtaposed or separated. EGF and TGF-α differ in their ability to maintain the conformation with the membrane-proximal tips of the extracellular module separated, and this conformation is stabilized preferentially by an oncogenic EGFR mutation. Close proximity of the transmembrane helices at the junction with the extracellular module has been associated previously with increased EGFR activity. Our results show how EGFR can couple the binding of different ligands to differential modulation of this proximity, thereby suggesting a molecular mechanism for the generation of ligand-sensitive differential outputs in this receptor family. 履歴 登録 2021年11月24日 登録サイト : RCSB / 処理サイト : RCSB改定 1.0 2021年12月22日 Provider : repository / タイプ : Initial release改定 1.1 2024年10月16日 Group : Data collection / Structure summaryカテゴリ : chem_comp_atom / chem_comp_bond ... chem_comp_atom / chem_comp_bond / em_admin / pdbx_entry_details / pdbx_modification_feature Item : _em_admin.last_update
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