登録情報 データベース : PDB / ID : 8hgo 構造の表示 ダウンロードとリンクタイトル The EGF-bound EGFR/HER2 ectodomain complex 要素(Epidermal growth ...) x 2 Receptor tyrosine-protein kinase erbB-2 詳細キーワード MEMBRANE PROTEIN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 cholesterol efflux / negative regulation of secretion / negative regulation of immature T cell proliferation in thymus / ERBB3:ERBB2 complex / ERBB2-ERBB4 signaling pathway / positive regulation of cerebellar granule cell precursor proliferation / GRB7 events in ERBB2 signaling / immature T cell proliferation in thymus / RNA polymerase I core binding ... positive regulation of hyaluronan biosynthetic process / negative regulation of cholesterol efflux / negative regulation of secretion / negative regulation of immature T cell proliferation in thymus / ERBB3:ERBB2 complex / ERBB2-ERBB4 signaling pathway / positive regulation of cerebellar granule cell precursor proliferation / GRB7 events in ERBB2 signaling / immature T cell proliferation in thymus / RNA polymerase I core binding / 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 / semaphorin receptor complex / regulation of calcium ion import / transmembrane receptor protein tyrosine kinase activator activity / Developmental Lineage of Pancreatic Acinar Cells / regulation of microtubule-based process / ErbB-3 class receptor binding / motor neuron axon guidance / positive regulation of ubiquitin-dependent protein catabolic process / Sema4D induced cell migration and growth-cone collapse / 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 / neurotransmitter receptor localization to postsynaptic specialization membrane / PTK6 promotes HIF1A stabilization / ERBB2 Activates PTK6 Signaling / branching morphogenesis of an epithelial tube / digestive tract morphogenesis / neuromuscular junction development / enzyme-linked receptor protein signaling pathway / Signaling by EGFR / ERBB2-ERBB3 signaling pathway / positive regulation of Rho protein signal transduction / response to cobalamin / 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 / negative regulation of epidermal growth factor receptor signaling pathway / positive regulation of transcription by RNA polymerase I / eyelid development in camera-type eye / cerebral cortex cell migration / protein insertion into membrane / ERBB2 Regulates Cell Motility / oligodendrocyte differentiation / semaphorin-plexin signaling pathway / protein tyrosine kinase activator 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 / positive regulation of phosphorylation / placental growth factor receptor activity / mammary gland alveolus development / hepatocyte growth factor receptor activity / boss receptor activity / stem cell factor receptor activity / platelet-derived growth factor beta-receptor activity / brain-derived neurotrophic factor receptor activity / positive regulation of peptidyl-serine phosphorylation / platelet-derived growth factor alpha-receptor activity / epidermal growth factor receptor activity / hair follicle development / positive regulation of protein targeting to membrane / macrophage colony-stimulating factor receptor activity 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 / Receptor tyrosine-protein kinase erbB-2 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 : 3.31 Å 詳細データ登録者 Zhang, Z. / Bai, X. 資金援助 中国, 1件 詳細 詳細を隠す組織 認可番号 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 登録サイト : PDBJ / 処理サイト : PDBJ改定 1.0 2023年2月8日 Provider : repository / タイプ : Initial release改定 1.1 2023年3月1日 Group : Database references / カテゴリ : citation / citation_authorItem : _citation.country / _citation.journal_abbrev ... _citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year 改定 1.2 2024年11月13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 / _pdbx_entry_details.has_protein_modification
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