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- PDB-9fk5: Zebrafish Betaglycan Orphan Domain (zfBGo) in complex with TGF-B3... -
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Open data
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Basic information
Entry | Database: PDB / ID: 9fk5 | |||||||||
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Title | Zebrafish Betaglycan Orphan Domain (zfBGo) in complex with TGF-B3 and extracellular domains of TGFBRI and TGFBRII | |||||||||
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![]() | MEMBRANE PROTEIN / Complex / Betaglycan / TGFBR3 / TGFb / TGFBR1 / TGFBR2 | |||||||||
Function / homology | ![]() 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 / mammary gland morphogenesis / detection of hypoxia / lens fiber cell apoptotic process / growth plate cartilage chondrocyte growth / transforming growth factor beta receptor activity, type II / 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 / secondary palate development / trophoblast cell migration / negative regulation of macrophage cytokine production / 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 / membranous septum morphogenesis / positive regulation of extracellular matrix assembly / TGFBR3 regulates TGF-beta signaling / 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 / coronary artery morphogenesis / filopodium assembly / embryonic cranial skeleton morphogenesis / ventricular trabecula myocardium morphogenesis / activin receptor signaling pathway / 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 / kinase activator activity / sprouting angiogenesis / collagen fibril organization / aortic valve morphogenesis / negative regulation of chondrocyte differentiation / lens development in camera-type eye / atrioventricular valve morphogenesis / endothelial cell activation / face morphogenesis / anterior/posterior pattern specification / odontogenesis / positive regulation of filopodium assembly / embryonic hemopoiesis / positive regulation of mesenchymal cell proliferation / artery morphogenesis / skeletal system morphogenesis Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.1 Å | |||||||||
![]() | Wieteska, L. / Coleman, J.A. / Hinck, A.P. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structures of TGF-β with betaglycan and signaling receptors reveal mechanisms of complex assembly and signaling. Authors: 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 ...Authors: 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 / ![]() ![]() ![]() ![]() Abstract: 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. | |||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 141.3 KB | Display | ![]() |
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PDB format | ![]() | 108 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 1.1 MB | Display | ![]() |
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Full document | ![]() | 1.1 MB | Display | |
Data in XML | ![]() | 41 KB | Display | |
Data in CIF | ![]() | 59.3 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 50519MC ![]() 9b9fC ![]() 9fdyC ![]() 9fkpC C: citing same article ( M: map data used to model this data |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 12734.504 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Protein | Mass: 12586.247 Da / Num. of mol.: 1 / Mutation: R325E,Y390A,R394E Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#3: Protein | Mass: 9474.826 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: P36897, receptor protein serine/threonine kinase |
#4: Protein | Mass: 12926.812 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: P37173, receptor protein serine/threonine kinase |
#5: Protein | Mass: 37727.000 Da / Num. of mol.: 1 / Mutation: C150G,C277G Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
Has protein modification | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
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Buffer solution | pH: 7.4 | ||||||||||||||||||||||||
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Specimen | Conc.: 0.3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: UltrAuFoil R1.2/1.3 | ||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 298 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 750 nm / Alignment procedure: COMA FREE |
Image recording | Electron dose: 45 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
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Processing
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4.1 Å / Resolution method: FSC 0.5 CUT-OFF / Num. of particles: 281881 / Symmetry type: POINT | ||||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 9B9F Accession code: 9B9F / Source name: PDB / Type: experimental model |