登録情報 データベース : PDB / ID : 9b9f 構造の表示 ダウンロードとリンクタイトル Zebrafish Betaglycan Orphan Domain (zfBGo) in complex with TGF-B3 and extracellular domains of TGFBRI and TGFBRII 要素Transforming growth factor beta receptor type-1 Transforming growth factor beta receptor type-2 Transforming growth factor beta receptor type-3 Transforming growth factor beta-3 Transforming growth factor beta-3 triple mutant 詳細キーワード MEMBRANE PROTEIN / Complex / Betaglycan / TGFBR3 / TGFb / TGFBR1 / TGFBR2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
FGFR1b ligand binding and activation / FGFR1c ligand binding and activation / TGF-beta receptor signaling activates SMADs / TGFBR3 PTM regulation / TGFBR3 regulates TGF-beta signaling / TGFBR3 regulates FGF2 signaling / positive regulation of tolerance induction to self antigen / positive regulation of B cell tolerance induction / uterine wall breakdown / inferior endocardial cushion morphogenesis ... FGFR1b ligand binding and activation / FGFR1c ligand binding and activation / TGF-beta receptor signaling activates SMADs / TGFBR3 PTM regulation / TGFBR3 regulates TGF-beta signaling / TGFBR3 regulates FGF2 signaling / positive regulation of tolerance induction to self antigen / positive regulation of B cell tolerance induction / uterine wall breakdown / inferior endocardial cushion morphogenesis / bronchus morphogenesis / transforming growth factor beta receptor activity, type II / mammary gland morphogenesis / detection of hypoxia / lens fiber cell apoptotic process / growth plate cartilage chondrocyte growth / tricuspid valve morphogenesis / extracellular structure organization / epicardium morphogenesis / vascular endothelial cell proliferation / TGFBR2 MSI Frameshift Mutants in Cancer / miRNA transport / parathyroid gland development / transforming growth factor beta ligand-receptor complex / regulation of cardiac muscle cell proliferation / aorta morphogenesis / type III transforming growth factor beta receptor binding / myofibroblast differentiation / positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation / Langerhans cell differentiation / TGFBR2 Kinase Domain Mutants in Cancer / transforming growth factor beta receptor activity / cardiac left ventricle morphogenesis / regulation of transforming growth factor beta receptor signaling pathway / negative regulation of macrophage cytokine production / secondary palate development / trophoblast cell migration / angiogenesis involved in coronary vascular morphogenesis / positive regulation of mesenchymal stem cell proliferation / SMAD2/3 Phosphorylation Motif Mutants in Cancer / TGFBR1 KD Mutants in Cancer / endocardial cushion fusion / positive regulation of T cell tolerance induction / ventricular compact myocardium morphogenesis / positive regulation of extracellular matrix assembly / TGFBR3 regulates TGF-beta signaling / membranous septum morphogenesis / positive regulation of tight junction disassembly / positive regulation of NK T cell differentiation / lung lobe morphogenesis / cardiac epithelial to mesenchymal transition / mesenchymal cell differentiation / somite development / positive regulation of vasculature development / transforming growth factor beta receptor activity, type I / neuron fate commitment / activin receptor complex / activin receptor activity, type I / regulation of epithelial to mesenchymal transition / type II transforming growth factor beta receptor binding / receptor protein serine/threonine kinase / transmembrane receptor protein serine/threonine kinase activity / pharyngeal system development / TGFBR1 LBD Mutants in Cancer / activin binding / regulation of stem cell proliferation / type I transforming growth factor beta receptor binding / SMAD protein signal transduction / germ cell migration / myeloid dendritic cell differentiation / filopodium assembly / coronary artery morphogenesis / embryonic cranial skeleton morphogenesis / activin receptor signaling pathway / ventricular trabecula myocardium morphogenesis / glycosaminoglycan binding / mammary gland development / positive regulation of CD4-positive, alpha-beta T cell proliferation / regulation of stem cell differentiation / outflow tract septum morphogenesis / response to cholesterol / I-SMAD binding / cell-cell junction organization / transforming growth factor beta binding / sprouting angiogenesis / collagen fibril organization / kinase activator activity / aortic valve morphogenesis / negative regulation of chondrocyte differentiation / lens development in camera-type eye / atrioventricular valve morphogenesis / endothelial cell activation / face morphogenesis / odontogenesis / positive regulation of filopodium assembly / anterior/posterior pattern specification / embryonic hemopoiesis / positive regulation of mesenchymal cell proliferation / artery morphogenesis / skeletal system morphogenesis 類似検索 - 分子機能 Transforming growth factor beta-3 / Transforming growth factor beta receptor 2 ectodomain / Transforming growth factor-beta receptor, type II / Transforming growth factor beta receptor 2 ectodomain / Transforming growth factor-beta / Zona pellucida domain, conserved site / ZP domain signature. / : / : / ZP-N domain ... Transforming growth factor beta-3 / Transforming growth factor beta receptor 2 ectodomain / Transforming growth factor-beta receptor, type II / Transforming growth factor beta receptor 2 ectodomain / Transforming growth factor-beta / Zona pellucida domain, conserved site / ZP domain signature. / : / : / ZP-N domain / Zona pellucida, ZP-C domain / ZP-C domain / Zona pellucida (ZP) domain / ZP domain profile. / Zona pellucida domain / GS domain / Transforming growth factor beta type I GS-motif / GS domain profile. / GS motif / TGF-beta, propeptide / TGF-beta propeptide / Activin types I and II receptor domain / Activin types I and II receptor domain / Transforming growth factor beta, conserved site / TGF-beta family signature. / Transforming growth factor-beta-related / Transforming growth factor-beta (TGF-beta) family / Transforming growth factor-beta, C-terminal / Transforming growth factor beta like domain / TGF-beta family profile. / Ser/Thr protein kinase, TGFB receptor / Cystine-knot cytokine / Snake toxin-like superfamily / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, 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 Transforming growth factor beta receptor III / Transforming growth factor beta-3 proprotein / TGF-beta receptor type-1 / TGF-beta receptor type-2 類似検索 - 構成要素生物種 Homo sapiens (ヒト)Danio rerio (ゼブラフィッシュ)手法 X線回折 / シンクロトロン / 分子置換 / 解像度 : 3 Å 詳細データ登録者 Wieteska, L. / Taylor, A.B. / Hinck, A.P. 資金援助 米国, European Union, 3件 詳細 詳細を隠す組織 認可番号 国 National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) GM058670 米国 H2020 Marie Curie Actions of the European Commission 893196 European Union National Institutes of Health/Office of the Director OD030374 米国
引用ジャーナル : Nat Commun / 年 : 2025タイトル : Structures of TGF-β with betaglycan and signaling receptors reveal mechanisms of complex assembly and signaling.著者: Łukasz Wieteska / Alexander B Taylor / Emma Punch / Jonathan A Coleman / Isabella O Conway / Yeu-Farn Lin / Chang-Hyeock Byeon / Cynthia S Hinck / Troy Krzysiak / Rieko Ishima / Fernando ... 著者 : Łukasz Wieteska / Alexander B Taylor / Emma Punch / Jonathan A Coleman / Isabella O Conway / Yeu-Farn Lin / Chang-Hyeock Byeon / Cynthia S Hinck / Troy Krzysiak / Rieko Ishima / Fernando López-Casillas / Peter Cherepanov / Daniel J Bernard / Caroline S Hill / Andrew P Hinck / 要旨 : Betaglycan (BG) is a transmembrane co-receptor of the transforming growth factor-β (TGF-β) family of signaling ligands. It is essential for embryonic development, tissue homeostasis and fertility ... Betaglycan (BG) is a transmembrane co-receptor of the transforming growth factor-β (TGF-β) family of signaling ligands. It is essential for embryonic development, tissue homeostasis and fertility in adults. It functions by enabling binding of the three TGF-β isoforms to their signaling receptors and is additionally required for inhibin A (InhA) activity. Despite its requirement for the functions of TGF-βs and InhA in vivo, structural information explaining BG ligand selectivity and its mechanism of action is lacking. Here, we determine the structure of TGF-β bound both to BG and the signaling receptors, TGFBR1 and TGFBR2. We identify key regions responsible for ligand engagement, which has revealed binding interfaces that differ from those described for the closely related co-receptor of the TGF-β family, endoglin, thus demonstrating remarkable evolutionary adaptation to enable ligand selectivity. Finally, we provide a structural explanation for the hand-off mechanism underlying TGF-β signal potentiation. 履歴 登録 2024年4月2日 登録サイト : RCSB / 処理サイト : RCSB改定 1.0 2025年3月12日 Provider : repository / タイプ : Initial release