[English] 日本語
Yorodumi
- EMDB-50333: Betaglycan Orphan Domain (ratBGo) in complex with TGF-b1 and extr... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-50333
TitleBetaglycan Orphan Domain (ratBGo) in complex with TGF-b1 and extracellular domain of TGFBRII
Map data
Sample
  • Complex: Ternary complex of Rat Betaglycan Orphan Domain (ratBGo) with TGF-B1 and extracellular domains of TGFBRII
    • Complex: Transforming growth factor beta-1
      • Protein or peptide: Transforming growth factor beta-1
    • Complex: Transforming growth factor beta receptor type-3, Orphan domain
      • Protein or peptide: Transforming growth factor beta receptor type 3
    • Complex: Transforming growth factor beta receptor type-2, extracellular domain
      • Protein or peptide: TGF-beta receptor type-2
KeywordsComplex / Betaglycan / TGFBR3 / TGFb1 / TGFBR2 / MEMBRANE PROTEIN
Function / homology
Function and homology information


TGFBR3 PTM regulation / TGFBR3 regulates FGF2 signaling / negative regulation of apoptotic process involved in morphogenesis / TGFBR3 regulates activin signaling / response to luteinizing hormone / FGFR1b ligand binding and activation / FGFR1c ligand binding and activation / TGF-beta receptor signaling activates SMADs / transforming growth factor beta receptor complex assembly / epicardium-derived cardiac fibroblast cell development ...TGFBR3 PTM regulation / TGFBR3 regulates FGF2 signaling / negative regulation of apoptotic process involved in morphogenesis / TGFBR3 regulates activin signaling / response to luteinizing hormone / FGFR1b ligand binding and activation / FGFR1c ligand binding and activation / TGF-beta receptor signaling activates SMADs / transforming growth factor beta receptor complex assembly / epicardium-derived cardiac fibroblast cell development / Signaling by BMP / inhibin-betaglycan-ActRII complex / muscular septum morphogenesis / positive regulation of tolerance induction to self antigen / positive regulation of B cell tolerance induction / inferior endocardial cushion morphogenesis / definitive erythrocyte differentiation / bronchus morphogenesis / cellular response to acetaldehyde / adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains / positive regulation of microglia differentiation / regulation of interleukin-23 production / branch elongation involved in mammary gland duct branching / positive regulation of primary miRNA processing / mammary gland morphogenesis / Influenza Virus Induced Apoptosis / response to follicle-stimulating hormone / lens fiber cell apoptotic process / TGFBR3 regulates TGF-beta signaling / growth plate cartilage chondrocyte growth / negative regulation of skeletal muscle tissue development / regulation of branching involved in mammary gland duct morphogenesis / tricuspid valve morphogenesis / macrophage derived foam cell differentiation / frontal suture morphogenesis / regulation of enamel mineralization / regulation of cartilage development / TGFBR2 MSI Frameshift Mutants in Cancer / regulation of striated muscle tissue development / regulatory T cell differentiation / tolerance induction to self antigen / regulation of blood vessel remodeling / miRNA transport / regulation of protein import into nucleus / BMP binding / embryonic liver development / extracellular matrix assembly / transforming growth factor beta ligand-receptor complex / negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target / vasculogenesis involved in coronary vascular morphogenesis / columnar/cuboidal epithelial cell maturation / negative regulation of hyaluronan biosynthetic process / type III transforming growth factor beta receptor binding / aorta morphogenesis / positive regulation of cardiac muscle cell differentiation / apoptotic process involved in morphogenesis / myofibroblast differentiation / positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation / odontoblast differentiation / positive regulation of odontogenesis / connective tissue replacement involved in inflammatory response wound healing / Langerhans cell differentiation / Signaling by Activin / negative regulation of macrophage cytokine production / positive regulation of smooth muscle cell differentiation / TGFBR2 Kinase Domain Mutants in Cancer / transforming growth factor beta receptor activity / positive regulation of exit from mitosis / ventricular compact myocardium morphogenesis / cardiac left ventricle morphogenesis / regulation of transforming growth factor beta receptor signaling pathway / secondary palate development / negative regulation of epithelial cell migration / positive regulation of isotype switching to IgA isotypes / positive regulation of mesenchymal stem cell proliferation / SMAD2/3 Phosphorylation Motif Mutants in Cancer / TGFBR1 KD Mutants in Cancer / endocardial cushion fusion / membrane protein intracellular domain proteolysis / positive regulation of receptor signaling pathway via STAT / positive regulation of T cell tolerance induction / membranous septum morphogenesis / heart valve morphogenesis / retina vasculature development in camera-type eye / TGFBR3 regulates TGF-beta signaling / lung lobe morphogenesis / mammary gland branching involved in thelarche / bronchiole development / hyaluronan catabolic process / positive regulation of NK T cell differentiation / cardiac epithelial to mesenchymal transition / positive regulation of vasculature development / response to laminar fluid shear stress / collagen metabolic process / activin receptor complex / lens fiber cell differentiation / positive regulation of extracellular matrix assembly / transforming growth factor beta receptor binding / negative regulation of extracellular matrix disassembly / ATP biosynthetic process
Similarity search - Function
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-1 proprotein / : / : / : / ZP-N domain / Transforming growth factor-beta / Zona pellucida domain, conserved site ...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-1 proprotein / : / : / : / ZP-N domain / Transforming growth factor-beta / Zona pellucida domain, conserved site / ZP domain signature. / Zona pellucida, ZP-C domain / ZP-C domain / Zona pellucida (ZP) domain / ZP domain profile. / Zona pellucida domain / TGF-beta, propeptide / TGF-beta propeptide / 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. / 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
Similarity search - Domain/homology
Transforming growth factor beta-1 proprotein / Transforming growth factor beta receptor type 3 / TGF-beta receptor type-2
Similarity search - Component
Biological speciesHomo sapiens (human) / Rattus norvegicus (Norway rat)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.4 Å
AuthorsWieteska L / Cherepanov P / Punch E / Hinck AP / Hill CS
Funding supportEuropean Union, United Kingdom, United States, 4 items
OrganizationGrant numberCountry
H2020 Marie Curie Actions of the European Commission893196European Union
The Francis Crick InstituteCC2021 United Kingdom
The Francis Crick InstituteCC2058 United Kingdom
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM058670 United States
CitationJournal: Nat Commun / Year: 2025
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
DepositionMay 17, 2024-
Header (metadata) releaseMar 12, 2025-
Map releaseMar 12, 2025-
UpdateMar 12, 2025-
Current statusMar 12, 2025Processing site: PDBe / Status: Released

-
Structure visualization

Supplemental images

emd_50333.png

Downloads & links

-
Map

FileDownload / File: emd_50333.map.gz / Format: CCP4 / Size: 83.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.92 Å/pix.
x 280 pix.
= 257.88 Å		0.92 Å/pix.
x 280 pix.
= 257.88 Å		0.92 Å/pix.
x 280 pix.
= 257.88 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.921 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.13
Minimum - Maximum-1.1916927 - 1.9097308
Average (Standard dev.)0.00045654344 (±0.030311292)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions280280280
Spacing280280280
CellA=B=C: 257.88 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Mask #1

Fileemd_50333_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Additional map: EMReady enhanced map

Fileemd_50333_additional_1.map
AnnotationEMReady enhanced map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Additional map: Maps with local filter applied

Fileemd_50333_additional_2.map
AnnotationMaps with local filter applied
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: Half map 1

Fileemd_50333_half_map_1.map
AnnotationHalf map 1
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: Half map 2

Fileemd_50333_half_map_2.map
AnnotationHalf map 2
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Ternary complex of Rat Betaglycan Orphan Domain (ratBGo) with TGF...

EntireName: Ternary complex of Rat Betaglycan Orphan Domain (ratBGo) with TGF-B1 and extracellular domains of TGFBRII
Components
  • Complex: Ternary complex of Rat Betaglycan Orphan Domain (ratBGo) with TGF-B1 and extracellular domains of TGFBRII
    • Complex: Transforming growth factor beta-1
      • Protein or peptide: Transforming growth factor beta-1
    • Complex: Transforming growth factor beta receptor type-3, Orphan domain
      • Protein or peptide: Transforming growth factor beta receptor type 3
    • Complex: Transforming growth factor beta receptor type-2, extracellular domain
      • Protein or peptide: TGF-beta receptor type-2

-
Supramolecule #1: Ternary complex of Rat Betaglycan Orphan Domain (ratBGo) with TGF...

SupramoleculeName: Ternary complex of Rat Betaglycan Orphan Domain (ratBGo) with TGF-B1 and extracellular domains of TGFBRII
type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 12 KDa

-
Supramolecule #2: Transforming growth factor beta-1

SupramoleculeName: Transforming growth factor beta-1 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

-
Supramolecule #3: Transforming growth factor beta receptor type-3, Orphan domain

SupramoleculeName: Transforming growth factor beta receptor type-3, Orphan domain
type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2
Source (natural)Organism: Rattus norvegicus (Norway rat)

-
Supramolecule #4: Transforming growth factor beta receptor type-2, extracellular domain

SupramoleculeName: Transforming growth factor beta receptor type-2, extracellular domain
type: complex / ID: 4 / Parent: 1 / Macromolecule list: #3
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Transforming growth factor beta-1

MacromoleculeName: Transforming growth factor beta-1 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 12.809812 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
ALDTNYCFSS TEKNCCVRQL YIDFRKDLGW KWIHEPKGYH ANFCLGPCPY IWSLDTQYSK VLALYNQHNP GASAAPCCVP QALEPLPIV YYVGRKPKVE QLSNMIVRSC KCS

UniProtKB: Transforming growth factor beta-1 proprotein

-
Macromolecule #2: Transforming growth factor beta receptor type 3

MacromoleculeName: Transforming growth factor beta receptor type 3 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Rattus norvegicus (Norway rat)
Molecular weightTheoretical: 38.109473 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: GSPCELSPIN ASHPVQALME SFTVLSGCAS RGTTGLPREV HVLNLRSTDQ GPGQRQREVT LHLNPIASVH THHKPIVFLL NSPQPLVWH LKTERLAAGV PRLFLVSEGS VVQFPSGNFS LTAETEERNF PQENEHLLRW AQKEYGAVTS FTELKIARNI Y IKVGEDQV ...String:
GSPCELSPIN ASHPVQALME SFTVLSGCAS RGTTGLPREV HVLNLRSTDQ GPGQRQREVT LHLNPIASVH THHKPIVFLL NSPQPLVWH LKTERLAAGV PRLFLVSEGS VVQFPSGNFS LTAETEERNF PQENEHLLRW AQKEYGAVTS FTELKIARNI Y IKVGEDQV FPPTCNIGKN FLSLNYLAEY LQPKAAEGCV LPSQPHEKEV HIIELITPSS NPYSAFQVDI IVDIRPAQED PE VVKNLVL ILKCKKSVNW VIKSFDVKGN LKVIAPNSIG FGKESERSMT MTKLVRDDIP STQENLMKWA LDNGYRPVTS YTM APVANR FHLRLENHHH HHH

UniProtKB: Transforming growth factor beta receptor type 3

-
Macromolecule #3: TGF-beta receptor type-2

MacromoleculeName: TGF-beta receptor type-2 / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO / EC number: receptor protein serine/threonine kinase
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 12.926812 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
MNGAVKFPQL CKFCDVRFST CDNQKSCMSN CSITSICEKP QEVCVAVWRK NDENITLETV CHDPKLPYHD FILEDAASPK CIMKEKKKP GETFFMCSCS SDECNDNIIF SEEY

UniProtKB: TGF-beta receptor type-2

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration0.6 mg/mL
BufferpH: 7.4
Component:
ConcentrationFormulaName
150.0 mMNaClsodium cholride
20.0 mMC8H18N2O4SHEPES
GridModel: UltrAuFoil R1.2/1.3 / Material: GOLD / Support film - Material: GRAPHENE OXIDE / Support film - topology: CONTINUOUS / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Number grids imaged: 1 / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.5 µm / Nominal defocus min: 1.5 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Particle selectionNumber selected: 4000000
Startup modelType of model: INSILICO MODEL
In silico model: In silico model (AF2M) validated on PDB: 3KFD for part of the complex
Final reconstructionAlgorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 4) / Number images used: 235089
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. v4)
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. v4)
Final 3D classificationSoftware - Name: RELION (ver. 4.0)
FSC plot (resolution estimation)

-
Atomic model buiding 1

Initial modelChain - Source name: AlphaFold / Chain - Initial model type: in silico model
RefinementSpace: REAL / Protocol: FLEXIBLE FIT
Output model

PDB-9fdy:
Betaglycan Orphan Domain (ratBGo) in complex with TGF-b1 and extracellular domain of TGFBRII

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more