登録情報 データベース : EMDB / ID : EMD-34746 ダウンロードとリンクタイトル The EGF-bound EGFR ectodomain homodimer マップデータ 詳細 試料複合体 : EGF-bound EGFR ectodomain homodimerタンパク質・ペプチド : Epidermal growth factor receptor 上皮成長因子受容体タンパク質・ペプチド : Pro-epidermal growth factorリガンド : 2-acetamido-2-deoxy-beta-D-glucopyranose 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
negative regulation of secretion / positive regulation of hyaluronan biosynthetic process / negative regulation of cholesterol efflux / positive regulation of cerebellar granule cell precursor proliferation / cerebellar granule cell precursor proliferation / positive regulation of epithelial tube formation / regulation of calcium ion import / positive regulation of protein localization to early endosome / regulation of protein localization to cell surface / positive regulation of ubiquitin-dependent protein catabolic process ... negative regulation of secretion / positive regulation of hyaluronan biosynthetic process / negative regulation of cholesterol efflux / positive regulation of cerebellar granule cell precursor proliferation / cerebellar granule cell precursor proliferation / positive regulation of epithelial tube formation / regulation of calcium ion import / positive regulation of protein localization to early endosome / regulation of protein localization to cell surface / positive regulation of ubiquitin-dependent protein catabolic process / response to hydroxyisoflavone / multivesicular body, internal vesicle lumen / positive regulation of prolactin secretion / negative regulation of cardiocyte differentiation / positive regulation of protein kinase C activity / diterpenoid metabolic process / regulation of receptor signaling pathway via JAK-STAT / Shc-EGFR complex / 月経周期 / Inhibition of Signaling by Overexpressed EGFR / epidermal growth factor receptor activity / EGFR interacts with phospholipase C-gamma / positive regulation of mucus secretion / response to UV-A / epidermal growth factor binding / PLCG1 events in ERBB2 signaling / tongue development / NFE2L2 regulating tumorigenic genes / midgut development / ERBB2-EGFR signaling pathway / hydrogen peroxide metabolic process / PTK6 promotes HIF1A stabilization / digestive tract morphogenesis / regulation of nitric-oxide synthase activity / epidermal growth factor receptor binding / morphogenesis of an epithelial fold / ERBB2 Activates PTK6 Signaling / branching morphogenesis of an epithelial tube / intracellular vesicle / Signaling by EGFR / response to cobalamin / transmembrane receptor protein tyrosine kinase activator activity / protein tyrosine kinase activator activity / negative regulation of epidermal growth factor receptor signaling pathway / Signaling by ERBB4 / regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / eyelid development in camera-type eye / protein insertion into membrane / cerebral cortex cell migration / ERBB2 Regulates Cell Motility / positive regulation of receptor internalization / regulation of JNK cascade / : / PI3K events in ERBB2 signaling / positive regulation of cyclin-dependent protein serine/threonine kinase activity / negative regulation of mitotic cell cycle / hair follicle development / MAP kinase kinase kinase activity / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / embryonic placenta development / mammary gland alveolus development / positive regulation of bone resorption / positive regulation of G1/S transition of mitotic cell cycle / positive regulation of DNA binding / GAB1 signalosome / positive regulation of nitric oxide mediated signal transduction / salivary gland morphogenesis / peptidyl-tyrosine autophosphorylation / regulation of peptidyl-tyrosine phosphorylation / positive regulation of phosphorylation / positive regulation of glial cell proliferation / positive regulation of vasoconstriction / Signaling by ERBB2 / cellular response to epidermal growth factor stimulus / positive regulation of endothelial cell proliferation / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / cellular response to cadmium ion / positive regulation of DNA repair / EGFR Transactivation by Gastrin / ERK1 and ERK2 cascade / GRB2 events in ERBB2 signaling / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / transmembrane receptor protein tyrosine kinase activity / SHC1 events in ERBB2 signaling / positive regulation of endothelial cell migration / 骨化 / positive regulation of mitotic nuclear division / positive regulation of synaptic transmission, glutamatergic / 神経発生 / cellular response to dexamethasone stimulus / guanyl-nucleotide exchange factor activity / basal plasma membrane / regulation of ERK1 and ERK2 cascade / neuron projection morphogenesis / positive regulation of superoxide anion generation / platelet alpha granule lumen / positive regulation of peptidyl-threonine phosphorylation / positive regulation of DNA replication / Signal transduction by L1 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 / Six-bladed beta-propeller, TolB-like / Tyrosine protein kinase, EGF/ERB/XmrK receptor ... 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 / Six-bladed beta-propeller, TolB-like / Tyrosine protein kinase, EGF/ERB/XmrK receptor / Growth factor receptor domain 4 / Growth factor receptor domain IV / Coagulation Factor Xa inhibitory site / 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 / EGF様ドメイン / EGF-like calcium-binding, conserved site / Calcium-binding EGF-like domain signature. / Furin-like repeat / Furin-like repeats / 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 2. / EGF-like domain signature 1. / EGF様ドメイン / 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. / 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 : 3.81 Å 詳細 データ登録者Zhang Z / Bai X 資金援助 中国, 1件 詳細 詳細を隠すOrganization Grant number 国 National Natural Science Foundation of China (NSFC) 32171201 中国
引用ジャーナル : Cell Discov / 年 : 2023タイトル : Structure and dynamics of the EGFR/HER2 heterodimer.著者 : Xue Bai / Pengyu Sun / Xinghao Wang / Changkun Long / Shuyun Liao / Song Dang / Shangshang Zhuang / Yongtao Du / Xinyi Zhang / Nan Li / Kangmin He / Zhe Zhang / 要旨 : HER2 belongs to the human epidermal growth factor receptor tyrosine kinase family. Its overexpression or hyperactivation is a leading cause for multiple types of cancers. HER2 functions mainly ... HER2 belongs to the human epidermal growth factor receptor tyrosine kinase family. Its overexpression or hyperactivation is a leading cause for multiple types of cancers. HER2 functions mainly through dimerization with other family members, such as EGFR. However, the molecular details for heterodimer assembly have not been completely understood. Here, we report cryo-EM structures of the EGF- and epiregulin-bound EGFR/HER2 ectodomain complexes at resolutions of 3.3 Å and 4.5 Å, respectively. Together with the functional analyses, we demonstrate that only the dimerization arm of HER2, but not that of EGFR, is essential for their heterodimer formation and signal transduction. Moreover, we analyze the differential membrane dynamics and transient interactions of endogenous EGFR and HER2 molecules in genome-edited cells using single-molecule live-cell imaging. Furthermore, we show that the interaction with HER2 could allow EGFR to resist endocytosis. Together, this work deepens our understanding of the unique structural properties and dynamics of the EGFR/HER2 complex. 履歴 登録 2022年11月15日 - ヘッダ(付随情報) 公開 2023年2月15日 - マップ公開 2023年2月15日 - 更新 2023年3月1日 - 現状 2023年3月1日 処理サイト : PDBj / 状態 : 公開
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