[English] 日本語
Yorodumi
- EMDB-43494: avb8/L-TGF-b1/GARP -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-43494
Titleavb8/L-TGF-b1/GARP
Map dataL-TGF-b1/GARP/avb8
Sample
  • Complex: avb8/L-TGF-b1/GARP complex
    • Complex: avb8 complex
      • Protein or peptide: Integrin alpha-V heavy chain
      • Protein or peptide: Integrin beta-8
    • Complex: L-TGF-b1/GARP complex
      • Protein or peptide: Transforming growth factor beta activator LRRC32
      • Protein or peptide: Transforming growth factor beta-1 proprotein
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: CALCIUM ION
  • Ligand: MAGNESIUM ION
KeywordsIntegrin / Complex / SIGNALING PROTEIN
Function / homology
Function and homology information


establishment of protein localization to extracellular region / ganglioside metabolic process / hard palate development / Langerhans cell differentiation / integrin alphav-beta8 complex / integrin alphav-beta6 complex / transforming growth factor beta production / negative regulation of entry of bacterium into host cell / integrin alphav-beta5 complex / secondary palate development ...establishment of protein localization to extracellular region / ganglioside metabolic process / hard palate development / Langerhans cell differentiation / integrin alphav-beta8 complex / integrin alphav-beta6 complex / transforming growth factor beta production / negative regulation of entry of bacterium into host cell / integrin alphav-beta5 complex / secondary palate development / extracellular matrix protein binding / opsonin binding / integrin alphav-beta1 complex / Cross-presentation of particulate exogenous antigens (phagosomes) / placenta blood vessel development / Laminin interactions / negative regulation of lipoprotein metabolic process / integrin alphav-beta3 complex / receptor ligand inhibitor activity / entry into host cell by a symbiont-containing vacuole / alphav-beta3 integrin-PKCalpha complex / alphav-beta3 integrin-HMGB1 complex / negative regulation of lipid transport / regulation of phagocytosis / : / Elastic fibre formation / alphav-beta3 integrin-IGF-1-IGF1R complex / transforming growth factor beta binding / positive regulation of small GTPase mediated signal transduction / filopodium membrane / extracellular matrix binding / apolipoprotein A-I-mediated signaling pathway / apoptotic cell clearance / wound healing, spreading of epidermal cells / integrin complex / heterotypic cell-cell adhesion / cartilage development / negative regulation of cytokine production / Molecules associated with elastic fibres / Mechanical load activates signaling by PIEZO1 and integrins in osteocytes / negative chemotaxis / cell adhesion mediated by integrin / Syndecan interactions / microvillus membrane / cell-substrate adhesion / positive regulation of osteoblast proliferation / negative regulation of activated T cell proliferation / endodermal cell differentiation / PECAM1 interactions / TGF-beta receptor signaling activates SMADs / positive regulation of intracellular signal transduction / lamellipodium membrane / fibronectin binding / negative regulation of macrophage derived foam cell differentiation / negative regulation of lipid storage / ECM proteoglycans / Integrin cell surface interactions / voltage-gated calcium channel activity / vasculogenesis / specific granule membrane / coreceptor activity / extrinsic apoptotic signaling pathway in absence of ligand / phagocytic vesicle / ERK1 and ERK2 cascade / extracellular matrix / positive regulation of cell adhesion / transforming growth factor beta receptor signaling pathway / substrate adhesion-dependent cell spreading / protein kinase C binding / Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells / cell-matrix adhesion / Signal transduction by L1 / integrin-mediated signaling pathway / negative regulation of extrinsic apoptotic signaling pathway / negative regulation of transforming growth factor beta receptor signaling pathway / calcium ion transmembrane transport / cell-cell adhesion / response to virus / VEGFA-VEGFR2 Pathway / ruffle membrane / positive regulation of angiogenesis / integrin binding / cell migration / virus receptor activity / positive regulation of cytosolic calcium ion concentration / protease binding / angiogenesis / cell adhesion / immune response / positive regulation of cell migration / symbiont entry into host cell / external side of plasma membrane / negative regulation of gene expression / focal adhesion / positive regulation of cell population proliferation / Neutrophil degranulation / positive regulation of gene expression / cell surface / extracellular space / extracellular exosome
Similarity search - Function
Teneurin-like EGF domain / Leucine rich repeat N-terminal domain / Leucine-rich repeat N-terminal domain / Leucine rich repeat N-terminal domain / Leucine rich repeat, ribonuclease inhibitor type / : / Integrin alpha Ig-like domain 3 / Integrin EGF domain / Integrins beta chain EGF (I-EGF) domain profile. / Integrin alpha cytoplasmic region ...Teneurin-like EGF domain / Leucine rich repeat N-terminal domain / Leucine-rich repeat N-terminal domain / Leucine rich repeat N-terminal domain / Leucine rich repeat, ribonuclease inhibitor type / : / Integrin alpha Ig-like domain 3 / Integrin EGF domain / Integrins beta chain EGF (I-EGF) domain profile. / Integrin alpha cytoplasmic region / Integrin beta subunit, VWA domain / Integrin beta subunit / Integrin beta N-terminal / Integrin beta chain VWA domain / Integrin plexin domain / Integrins beta chain EGF (I-EGF) domain signature. / Integrin beta subunits (N-terminal portion of extracellular region) / Integrin alpha-2 / Integrin alpha Ig-like domain 1 / Integrin alpha chain / Integrin alpha beta-propellor / Integrin alpha chain, C-terminal cytoplasmic region, conserved site / : / Integrin alpha Ig-like domain 2 / Integrins alpha chain signature. / FG-GAP repeat profile. / Integrin alpha (beta-propellor repeats). / FG-GAP repeat / FG-GAP repeat / Integrin domain superfamily / Integrin alpha, N-terminal / Leucine-rich repeats, bacterial type / PSI domain / domain found in Plexins, Semaphorins and Integrins / Leucine rich repeat / Leucine-rich repeat, typical subtype / Leucine-rich repeats, typical (most populated) subfamily / Leucine-rich repeat profile. / von Willebrand factor A-like domain superfamily / EGF-like domain signature 1. / EGF-like domain signature 2. / EGF-like domain / Leucine-rich repeat / Leucine-rich repeat domain superfamily
Similarity search - Domain/homology
Integrin alpha-V / Integrin beta-8 / Transforming growth factor beta activator LRRC32
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsJin M / Cheng Y / Nishimura SL
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)HL134183 United States
CitationJournal: Cell / Year: 2024
Title: Dynamic allostery drives autocrine and paracrine TGF-β signaling.
Authors: Mingliang Jin / Robert I Seed / Guoqing Cai / Tiffany Shing / Li Wang / Saburo Ito / Anthony Cormier / Stephanie A Wankowicz / Jillian M Jespersen / Jody L Baron / Nicholas D Carey / Melody ...Authors: Mingliang Jin / Robert I Seed / Guoqing Cai / Tiffany Shing / Li Wang / Saburo Ito / Anthony Cormier / Stephanie A Wankowicz / Jillian M Jespersen / Jody L Baron / Nicholas D Carey / Melody G Campbell / Zanlin Yu / Phu K Tang / Pilar Cossio / Weihua Wen / Jianlong Lou / James Marks / Stephen L Nishimura / Yifan Cheng /
Abstract: TGF-β, essential for development and immunity, is expressed as a latent complex (L-TGF-β) non-covalently associated with its prodomain and presented on immune cell surfaces by covalent association ...TGF-β, essential for development and immunity, is expressed as a latent complex (L-TGF-β) non-covalently associated with its prodomain and presented on immune cell surfaces by covalent association with GARP. Binding to integrin αvβ8 activates L-TGF-β1/GARP. The dogma is that mature TGF-β must physically dissociate from L-TGF-β1 for signaling to occur. Our previous studies discovered that αvβ8-mediated TGF-β autocrine signaling can occur without TGF-β1 release from its latent form. Here, we show that mice engineered to express TGF-β1 that cannot release from L-TGF-β1 survive without early lethal tissue inflammation, unlike those with TGF-β1 deficiency. Combining cryogenic electron microscopy with cell-based assays, we reveal a dynamic allosteric mechanism of autocrine TGF-β1 signaling without release where αvβ8 binding redistributes the intrinsic flexibility of L-TGF-β1 to expose TGF-β1 to its receptors. Dynamic allostery explains the TGF-β3 latency/activation mechanism and why TGF-β3 functions distinctly from TGF-β1, suggesting that it broadly applies to other flexible cell surface receptor/ligand systems.
History
DepositionJan 23, 2024-
Header (metadata) releaseSep 11, 2024-
Map releaseSep 11, 2024-
UpdateNov 20, 2024-
Current statusNov 20, 2024Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_43494.png

Downloads & links

-
Map

FileDownload / File: emd_43494.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationL-TGF-b1/GARP/avb8
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.17 Å/pix.
x 512 pix.
= 601.19 Å		1.17 Å/pix.
x 512 pix.
= 601.19 Å		1.17 Å/pix.
x 512 pix.
= 601.19 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.1742 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.4
Minimum - Maximum-1.4487923 - 2.5538673
Average (Standard dev.)-0.00048373707 (±0.058661763)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions512512512
Spacing512512512
CellA=B=C: 601.1904 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Sample components

+
Entire : avb8/L-TGF-b1/GARP complex

EntireName: avb8/L-TGF-b1/GARP complex
Components
  • Complex: avb8/L-TGF-b1/GARP complex
    • Complex: avb8 complex
      • Protein or peptide: Integrin alpha-V heavy chain
      • Protein or peptide: Integrin beta-8
    • Complex: L-TGF-b1/GARP complex
      • Protein or peptide: Transforming growth factor beta activator LRRC32
      • Protein or peptide: Transforming growth factor beta-1 proprotein
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: CALCIUM ION
  • Ligand: MAGNESIUM ION

+
Supramolecule #1: avb8/L-TGF-b1/GARP complex

SupramoleculeName: avb8/L-TGF-b1/GARP complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 / Details: mixture of avb8 and L-TGF-b1/GARP
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 180 KDa

+
Supramolecule #2: avb8 complex

SupramoleculeName: avb8 complex / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #2-#3
Source (natural)Organism: Homo sapiens (human)

+
Supramolecule #3: L-TGF-b1/GARP complex

SupramoleculeName: L-TGF-b1/GARP complex / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #1, #4
Source (natural)Organism: Homo sapiens (human)

+
Macromolecule #1: Transforming growth factor beta activator LRRC32

MacromoleculeName: Transforming growth factor beta activator LRRC32 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 61.344055 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: CKMVDKKVSC QVLGLLQVPS VLPPDTETLD LSGNQLRSIL ASPLGFYTAL RHLDLSTNEI SFLQPGAFQA LTHLEHLSLA HNRLAMATA LSAGGLGPLP RVTSLDLSGN SLYSGLLERL LGEAPSLHTL SLAENSLTRL TRHTFRDMPA LEQLDLHSNV L MDIEDGAF ...String:
CKMVDKKVSC QVLGLLQVPS VLPPDTETLD LSGNQLRSIL ASPLGFYTAL RHLDLSTNEI SFLQPGAFQA LTHLEHLSLA HNRLAMATA LSAGGLGPLP RVTSLDLSGN SLYSGLLERL LGEAPSLHTL SLAENSLTRL TRHTFRDMPA LEQLDLHSNV L MDIEDGAF EGLPRLTHLN LSRNSLTCIS DFSLQQLRVL DLSCNSIEAF QTASQPQAEF QLTWLDLREN KLLHFPDLAA LP RLIYLNL SNNLIRLPTG PPQDSKGIHA PSEGWSALPL SAPSGNASGR PLSQLLNLDL SYNEIELIPD SFLEHLTSLC FLN LSRNCL RTFEARRLGS LPCLMLLDLS HNALETLELG ARALGSLRTL LLQGNALRDL PPYTFANLAS LQRLNLQGNR VSPC GGPDE PGPSGCVAFS GITSLRSLSL VDNEIELLRA GAFLHTPLTE LDLSSNPGLE VATGALGGLE ASLEVLALQG NGLMV LQVD LPCFICLKRL NLAENRLSHL PAWTQAVSLE VLDLRNNSFS LLPGSAMGGL ETSLRRLYLQ GNPLSCCGNG WLAAQL HQG RVD

UniProtKB: Transforming growth factor beta activator LRRC32

+
Macromolecule #2: Integrin alpha-V heavy chain

MacromoleculeName: Integrin alpha-V heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 65.268188 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString: FNLDVDSPAE YSGPEGSYFG FAVDFFVPSA SSRMFLLVGA PKANTTQPGI VEGGQVLKCD WSSTRRCQPI EFDATGNRDY AKDDPLEFK SHQWFGASVR SKQDKILACA PLYHWRTEMK QEREPVGTCF LQDGTKTVEY APCRSQDIDA DGQGFCQGGF S IDFTKADR ...String:
FNLDVDSPAE YSGPEGSYFG FAVDFFVPSA SSRMFLLVGA PKANTTQPGI VEGGQVLKCD WSSTRRCQPI EFDATGNRDY AKDDPLEFK SHQWFGASVR SKQDKILACA PLYHWRTEMK QEREPVGTCF LQDGTKTVEY APCRSQDIDA DGQGFCQGGF S IDFTKADR VLLGGPGSFY WQGQLISDQV AEIVSKYDPN VYSIKYNNQL ATRTAQAIFD DSYLGYSVAV GDFNGDGIDD FV SGVPRAA RTLGMVYIYD GKNMSSLYNF TGEQMAAYFG FSVAATDING DDYADVFIGA PLFMDRGSDG KLQEVGQVSV SLQ RASGDF QTTKLNGFEV FARFGSAIAP LGDLDQDGFN DIAIAAPYGG EDKKGIVYIF NGRSTGLNAV PSQILEGQWA ARSM PPSFG YSMKGATDID KNGYPDLIVG AFGVDRAILY RARPVITVNA GLEVYPSILN QDNKTCSLPG TALKVSCFNV RFCLK ADGK GVLPRKLNFQ VELLLDKLKQ KGAIRRALFL YSRSPSHSKN MTISRGGLMQ CEELIAYLRD ESEFRDKLTP ITIFME YRL DYRTAADTTG LQPILNQFTP ANISRQAHIL

UniProtKB: Integrin alpha-V

+
Macromolecule #3: Integrin beta-8

MacromoleculeName: Integrin beta-8 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 39.574234 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString: INTQVTPGEV SIQLRPGAEA NFMLKVHPLK KYPVDLYYLV DVSASMHNNI EKLNSVGNDL SRKMAFFSRD FRLGFGSYVD KTVSPYISI HPERIHNQCS DYNLDCMPPH GYIHVLSLTE NITEFEKAVH RQKISGNIDT PEGGFDAMLQ AAVCESHIGW R KEAKRLLL ...String:
INTQVTPGEV SIQLRPGAEA NFMLKVHPLK KYPVDLYYLV DVSASMHNNI EKLNSVGNDL SRKMAFFSRD FRLGFGSYVD KTVSPYISI HPERIHNQCS DYNLDCMPPH GYIHVLSLTE NITEFEKAVH RQKISGNIDT PEGGFDAMLQ AAVCESHIGW R KEAKRLLL VMTDQTSHLA LDSKLAGIVV PNDGNCHLKN NVYVKSTTME HPSLGQLSEK LIDNNINVIF AVQGKQFHWY KD LLPLLPG TIAGEIESKA ANLNNLVVEA YQKLISEVKV QVENQVQGIY FNITAICPDG SRKPGMEGCR NVTSNDEVLF NVT VTMKKC DVTGGKNYAI IKPIGFNETA KIHIHRNC

UniProtKB: Integrin beta-8

+
Macromolecule #4: Transforming growth factor beta-1 proprotein

MacromoleculeName: Transforming growth factor beta-1 proprotein / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 41.323219 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: LSTCKTIDME LVKRKRIEAI RGQILSKLRL ASPPSQGEVP PGPLPEAVLA LYNSTRDRVA GESAEPEPEP EADYYAKEVT RVLMVETHN EIYDKFKQST HSIYMFFNTS ELREAVPEPV LLSRAELRLL RLKLKVEQHV ELYQKYSNNS WRYLSNRLLA P SDSPEWLS ...String:
LSTCKTIDME LVKRKRIEAI RGQILSKLRL ASPPSQGEVP PGPLPEAVLA LYNSTRDRVA GESAEPEPEP EADYYAKEVT RVLMVETHN EIYDKFKQST HSIYMFFNTS ELREAVPEPV LLSRAELRLL RLKLKVEQHV ELYQKYSNNS WRYLSNRLLA P SDSPEWLS FDVTGVVRQW LSRGGEIEGF RLSAHCSCDS RDNTLQVDIN GFTTGRRGDL ATIHGMNRPF LLLMATPLER AQ HLQSSRH RRALDTNYCF SSTEKNCCVR QLYIDFRKDL GWKWIHEPKG YHANFCLGPC PYIWSLDTQY SKVLALYNQH NPG ASAAPC CVPQALEPLP IVYYVGRKPK VEQLSNMIVR SCKCS

+
Macromolecule #7: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 7 / Number of copies: 3 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

+
Macromolecule #8: CALCIUM ION

MacromoleculeName: CALCIUM ION / type: ligand / ID: 8 / Number of copies: 5 / Formula: CA
Molecular weightTheoretical: 40.078 Da

+
Macromolecule #9: MAGNESIUM ION

MacromoleculeName: MAGNESIUM ION / type: ligand / ID: 9 / Number of copies: 1 / Formula: MG
Molecular weightTheoretical: 24.305 Da

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.4
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 68.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 46771
Initial angle assignmentType: NOT APPLICABLE
Final angle assignmentType: NOT APPLICABLE

+
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