登録情報 データベース : EMDB / ID : EMD-34745 ダウンロードとリンクタイトル The EREG-bound EGFR/HER2 ectodomain complex マップデータ 詳細 試料複合体 : EREG-bound EGFR/HER2 ectodomain complexタンパク質・ペプチド : Receptor tyrosine-protein kinase erbB-2タンパク質・ペプチド : Epidermal growth factor receptorタンパク質・ペプチド : Proepiregulin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
luteinizing hormone signaling pathway / ovarian cumulus expansion / ovulation / ERBB4-ERBB4 signaling pathway / negative regulation of smooth muscle cell differentiation / negative regulation of immature T cell proliferation in thymus / ERBB3:ERBB2 complex / ERBB2-ERBB4 signaling pathway / GRB7 events in ERBB2 signaling / immature T cell proliferation in thymus ... luteinizing hormone signaling pathway / ovarian cumulus expansion / ovulation / ERBB4-ERBB4 signaling pathway / negative regulation of smooth muscle cell differentiation / negative regulation of immature T cell proliferation in thymus / ERBB3:ERBB2 complex / ERBB2-ERBB4 signaling pathway / GRB7 events in ERBB2 signaling / immature T cell proliferation in thymus / RNA polymerase I core binding / primary follicle stage / female meiotic nuclear division / semaphorin receptor complex / PI3K events in ERBB4 signaling / regulation of microtubule-based process / ErbB-3 class receptor binding / positive regulation of innate immune response / Sema4D induced cell migration and growth-cone collapse / motor neuron axon guidance / 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 / mRNA transcription / diterpenoid metabolic process / Shc-EGFR complex / ovulation cycle / oocyte maturation / 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 / neurotransmitter receptor localization to postsynaptic specialization membrane / PLCG1 events in ERBB2 signaling / tongue development / midgut development / ERBB2-EGFR signaling pathway / hydrogen peroxide metabolic process / PTK6 promotes HIF1A stabilization / positive regulation of Rho protein signal transduction / digestive tract morphogenesis / epidermal growth factor receptor binding / regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / neuromuscular junction development / morphogenesis of an epithelial fold / ERBB2 Activates PTK6 Signaling / intracellular vesicle / Drug-mediated inhibition of ERBB2 signaling / Resistance of ERBB2 KD mutants to trastuzumab / Resistance of ERBB2 KD mutants to sapitinib / Resistance of ERBB2 KD mutants to tesevatinib / Resistance of ERBB2 KD mutants to neratinib / Resistance of ERBB2 KD mutants to osimertinib / Resistance of ERBB2 KD mutants to afatinib / Resistance of ERBB2 KD mutants to AEE788 / Resistance of ERBB2 KD mutants to lapatinib / Drug resistance in ERBB2 TMD/JMD mutants / Signaling by EGFR / response to cobalamin / enzyme-linked receptor protein signaling pathway / transmembrane receptor protein tyrosine kinase activator activity / ERBB2-ERBB3 signaling pathway / positive regulation of transcription by RNA polymerase I / protein tyrosine kinase activator activity / negative regulation of epidermal growth factor receptor signaling pathway / Signaling by ERBB4 / eyelid development in camera-type eye / protein insertion into membrane / oligodendrocyte differentiation / cerebral cortex cell migration / ERBB2 Regulates Cell Motility / Respiratory syncytial virus (RSV) attachment and entry / regulation of JNK cascade / semaphorin-plexin signaling pathway / positive regulation of cell division / : / PI3K events in ERBB2 signaling / positive regulation of cyclin-dependent protein serine/threonine kinase activity / keratinocyte proliferation / positive regulation of cell adhesion / negative regulation of mitotic cell cycle / hair follicle development / SHC1 events in ERBB4 signaling / MAP kinase kinase kinase activity / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / positive regulation of protein targeting to membrane / anatomical structure morphogenesis / embryonic placenta development / positive regulation of protein kinase activity / positive regulation of bone resorption / GAB1 signalosome / positive regulation of G1/S transition of mitotic cell cycle / regulation of angiogenesis / coreceptor activity / Schwann cell development / salivary gland morphogenesis 類似検索 - 分子機能 : / Epidermal growth factor receptor transmembrane-juxtamembrane segment / Tyrosine protein kinase, EGF/ERB/XmrK receptor / Growth factor receptor domain 4 / Growth factor receptor domain IV / Receptor L-domain / Furin-like cysteine-rich domain / Receptor L-domain superfamily / Furin-like cysteine rich region / Receptor L 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 / 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 / EGF-like domain profile. / Growth factor receptor cysteine-rich domain superfamily / : / EGF-like domain signature 2. / EGF-like domain signature 1. / EGF-like domain / 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 Proepiregulin / Epidermal growth factor receptor / Receptor tyrosine-protein kinase erbB-2 類似検索 - 構成要素生物種 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 : 4.53 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8日 - マップ公開 2023年2月8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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