登録情報 データベース : EMDB / ID : EMD-41883 ダウンロードとリンクタイトル Structure of the HER4/NRG1b Homodimer Extracellular Domain マップデータ 詳細 試料複合体 : HER4/NRG1b homodimerタンパク質・ペプチド : Receptor tyrosine-protein kinase erbB-4タンパク質・ペプチド : Isoform 6 of Pro-neuregulin-1, membrane-bound isoformリガンド : 2-acetamido-2-deoxy-beta-D-glucopyranose 詳細 キーワード Receptor Tyrosine Kinase / MEMBRANE PROTEIN / TRANSFERASE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
ERBB3 signaling pathway / positive regulation of peptidyl-tyrosine autophosphorylation / sequestering of metal ion / establishment of planar polarity involved in nephron morphogenesis / ERBB4 signaling pathway / ERBB4-ERBB4 signaling pathway / central nervous system morphogenesis / olfactory bulb interneuron differentiation / ventricular cardiac muscle cell differentiation / positive regulation of striated muscle cell differentiation ... ERBB3 signaling pathway / positive regulation of peptidyl-tyrosine autophosphorylation / sequestering of metal ion / establishment of planar polarity involved in nephron morphogenesis / ERBB4 signaling pathway / ERBB4-ERBB4 signaling pathway / central nervous system morphogenesis / olfactory bulb interneuron differentiation / ventricular cardiac muscle cell differentiation / positive regulation of striated muscle cell differentiation / neuregulin receptor activity / negative regulation of secretion / cardiac muscle tissue regeneration / endocardial cell differentiation / animal organ development / ERBB2-ERBB4 signaling pathway / GRB7 events in ERBB2 signaling / mitochondrial fragmentation involved in apoptotic process / neural crest cell development / embryonic pattern specification / cardiac muscle cell myoblast differentiation / mammary gland development / GABA receptor binding / cell communication / PI3K events in ERBB4 signaling / cardiac muscle cell differentiation / mammary gland epithelial cell differentiation / chemorepellent activity / ventricular trabecula myocardium morphogenesis / ErbB-3 class receptor binding / positive regulation of protein localization to cell surface / regulation of postsynaptic neurotransmitter receptor internalization / neural crest cell migration / activation of transmembrane receptor protein tyrosine kinase activity / epidermal growth factor receptor activity / ERBB signaling pathway / neurotransmitter receptor localization to postsynaptic specialization membrane / negative regulation of cardiac muscle cell apoptotic process / epidermal growth factor receptor binding / ERBB2 Activates PTK6 Signaling / transmembrane receptor protein tyrosine kinase activator activity / protein tyrosine kinase activator activity / ERBB2-ERBB3 signaling pathway / Signaling by ERBB4 / ERBB2 Regulates Cell Motility / cell surface receptor signaling pathway via JAK-STAT / Long-term potentiation / PI3K events in ERBB2 signaling / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / SHC1 events in ERBB4 signaling / cell fate commitment / mammary gland alveolus development / positive regulation of tyrosine phosphorylation of STAT protein / positive regulation of cardiac muscle cell proliferation / GABA-ergic synapse / cell surface receptor protein tyrosine kinase signaling pathway / Nuclear signaling by ERBB4 / Signaling by ERBB2 / synapse assembly / cellular response to epidermal growth factor stimulus / transmembrane receptor protein tyrosine kinase activity / lactation / activation of protein kinase B activity / GRB2 events in ERBB2 signaling / regulation of cell migration / Downregulation of ERBB4 signaling / neurogenesis / SHC1 events in ERBB2 signaling / positive regulation of cell adhesion / Downregulation of ERBB2:ERBB3 signaling / basal plasma membrane / cytokine activity / positive regulation of receptor signaling pathway via JAK-STAT / Signaling by ERBB2 TMD/JMD mutants / transcription coregulator activity / postsynaptic density membrane / growth factor activity / positive regulation of protein-containing complex assembly / wound healing / receptor protein-tyrosine kinase / neuromuscular junction / Signaling by ERBB2 KD Mutants / receptor tyrosine kinase binding / peptidyl-tyrosine phosphorylation / Downregulation of ERBB2 signaling / Constitutive Signaling by Aberrant PI3K in Cancer / cell migration / integrin binding / PIP3 activates AKT signaling / heart development / nervous system development / presynaptic membrane / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / RAF/MAP kinase cascade / positive regulation of cell growth / protein tyrosine kinase activity / basolateral plasma membrane / postsynaptic membrane / Estrogen-dependent gene expression / protein autophosphorylation 類似検索 - 分子機能 Neuregulin, C-terminal / Neuregulin-1 / Neuregulin / Neuregulin intracellular region / : / 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 ... Neuregulin, C-terminal / Neuregulin-1 / Neuregulin / Neuregulin intracellular region / : / 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 / EGF-like domain / Furin-like repeat / Furin-like repeats / Immunoglobulin I-set / Immunoglobulin I-set 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-like domain / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Immunoglobulin subtype / Immunoglobulin / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / 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 Pro-neuregulin-1, membrane-bound isoform / Receptor tyrosine-protein kinase erbB-4 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 : 3.38 Å 詳細 データ登録者Trenker R / Diwanji D / Bingham T / Verba KA / Jura N 資金援助 ドイツ, 米国, 3件 詳細 詳細を隠すOrganization Grant number 国 German Research Foundation (DFG) TR 1668/1-1 ドイツ National Institutes of Health/National Cancer Institute (NIH/NCI) CA274502 米国 National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) GM139636 米国
引用ジャーナル : Elife / 年 : 2024タイトル : Structural dynamics of the active HER4 and HER2/HER4 complexes is finely tuned by different growth factors and glycosylation.著者 : Raphael Trenker / Devan Diwanji / Tanner Bingham / Kliment A Verba / Natalia Jura / 要旨 : Human Epidermal growth factor Receptor 4 (HER4 or ERBB4) carries out essential functions in the development and maintenance of the cardiovascular and nervous systems. HER4 activation is regulated by ... Human Epidermal growth factor Receptor 4 (HER4 or ERBB4) carries out essential functions in the development and maintenance of the cardiovascular and nervous systems. HER4 activation is regulated by a diverse group of extracellular ligands including the neuregulin (NRG) family and betacellulin (BTC), which promote HER4 homodimerization or heterodimerization with other HER receptors. Important cardiovascular functions of HER4 are exerted via heterodimerization with its close homolog and orphan receptor, HER2. To date structural insights into ligand-mediated HER4 activation have been limited to crystallographic studies of HER4 ectodomain homodimers in complex with NRG1β. Here, we report cryo-EM structures of near full-length HER2/HER4 heterodimers and full-length HER4 homodimers bound to NRG1β and BTC. We show that the structures of the heterodimers bound to either ligand are nearly identical and that in both cases the HER2/HER4 heterodimer interface is less dynamic than those observed in structures of HER2/EGFR and HER2/HER3 heterodimers. In contrast, structures of full-length HER4 homodimers bound to NRG1β and BTC display more large-scale dynamics mirroring states previously reported for EGFR homodimers. Our structures also reveal the presence of multiple glycan modifications within HER4 ectodomains, modeled for the first time in HER receptors, that distinctively contribute to the stabilization of HER4 homodimer interfaces over those of HER2/HER4 heterodimers. 履歴 登録 2023年9月10日 - ヘッダ(付随情報) 公開 2024年3月13日 - マップ公開 2024年3月13日 - 更新 2024年9月25日 - 現状 2024年9月25日 処理サイト : RCSB / 状態 : 公開
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