[English] 日本語
Yorodumi
- PDB-8c7h: Cryo-EM Map of the latTGF-beta LHG-10 Fab complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8c7h
TitleCryo-EM Map of the latTGF-beta LHG-10 Fab complex
Components
  • (Transforming growth factor beta- ...) x 2
  • 28G11 Fab heavy chain
  • 28G11 Fab light chain
  • Transforming growth factor beta activator LRRC32
KeywordsIMMUNE SYSTEM / Fab-complex / GARP / lat-TGF-beta
Function / homology
Function and homology information


establishment of protein localization to extracellular region / cellular response to acetaldehyde / frontal suture morphogenesis / Influenza Virus Induced Apoptosis / 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 / columnar/cuboidal epithelial cell maturation ...establishment of protein localization to extracellular region / cellular response to acetaldehyde / frontal suture morphogenesis / Influenza Virus Induced Apoptosis / 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 / columnar/cuboidal epithelial cell maturation / negative regulation of skeletal muscle tissue development / embryonic liver development / macrophage derived foam cell differentiation / response to laminar fluid shear stress / regulation of enamel mineralization / regulation of branching involved in mammary gland duct morphogenesis / regulation of cartilage development / TGFBR2 MSI Frameshift Mutants in Cancer / regulation of striated muscle tissue development / regulation of blood vessel remodeling / regulation of protein import into nucleus / regulatory T cell differentiation / tolerance induction to self antigen / extracellular matrix assembly / negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target / negative regulation of hyaluronan biosynthetic process / type III transforming growth factor beta receptor binding / myofibroblast differentiation / positive regulation of cardiac muscle cell differentiation / positive regulation of odontogenesis / connective tissue replacement involved in inflammatory response wound healing / Langerhans cell differentiation / TGFBR2 Kinase Domain Mutants in Cancer / positive regulation of smooth muscle cell differentiation / positive regulation of exit from mitosis / secondary palate development / negative regulation of macrophage cytokine production / odontoblast differentiation / SMAD2/3 Phosphorylation Motif Mutants in Cancer / TGFBR1 KD Mutants in Cancer / positive regulation of isotype switching to IgA isotypes / positive regulation of mesenchymal stem cell proliferation / positive regulation of receptor signaling pathway via STAT / membrane protein intracellular domain proteolysis / positive regulation of extracellular matrix assembly / retina vasculature development in camera-type eye / heart valve morphogenesis / bronchiole development / TGFBR3 regulates TGF-beta signaling / mammary gland branching involved in thelarche / hyaluronan catabolic process / positive regulation of vasculature development / lens fiber cell differentiation / ATP biosynthetic process / negative regulation of extracellular matrix disassembly / type II transforming growth factor beta receptor binding / receptor catabolic process / positive regulation of branching involved in ureteric bud morphogenesis / positive regulation of chemotaxis / TGFBR1 LBD Mutants in Cancer / receptor ligand inhibitor activity / type I transforming growth factor beta receptor binding / positive regulation of mononuclear cell migration / response to salt / germ cell migration / endoderm development / negative regulation of biomineral tissue development / phospholipid homeostasis / negative regulation of cell-cell adhesion mediated by cadherin / negative regulation of myoblast differentiation / positive regulation of vascular permeability / response to cholesterol / oligodendrocyte development / cell-cell junction organization / negative regulation of interleukin-17 production / phosphate-containing compound metabolic process / surfactant homeostasis / transforming growth factor beta binding / deubiquitinase activator activity / sprouting angiogenesis / negative regulation of release of sequestered calcium ion into cytosol / negative regulation of ossification / positive regulation of chemokine (C-X-C motif) ligand 2 production / digestive tract development / aortic valve morphogenesis / RUNX3 regulates CDKN1A transcription / response to vitamin D / face morphogenesis / positive regulation of fibroblast migration / ureteric bud development / neural tube development / positive regulation of regulatory T cell differentiation / positive regulation of peptidyl-tyrosine phosphorylation / Molecules associated with elastic fibres / negative regulation of phagocytosis / positive regulation of epidermal growth factor receptor signaling pathway / negative regulation of neuroblast proliferation / negative regulation of cytokine production / lung alveolus development / Syndecan interactions
Similarity search - Function
Transforming growth factor beta-1 proprotein / Transforming growth factor-beta / TGF-beta, propeptide / TGF-beta propeptide / Leucine rich repeat N-terminal 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-1 proprotein / Transforming growth factor-beta / TGF-beta, propeptide / TGF-beta propeptide / Leucine rich repeat N-terminal 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. / Leucine-rich repeat N-terminal domain / Leucine rich repeat N-terminal domain / Leucine rich repeat, ribonuclease inhibitor type / Leucine-rich repeats, bacterial type / Cystine-knot cytokine / Leucine rich repeat / Leucine-rich repeat, typical subtype / Leucine-rich repeats, typical (most populated) subfamily / Leucine-rich repeat profile. / Leucine-rich repeat / Leucine-rich repeat domain superfamily / Immunoglobulins / Immunoglobulin-like / Sandwich / Mainly Beta
Similarity search - Domain/homology
Transforming growth factor beta-1 proprotein / Transforming growth factor beta activator LRRC32
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.7 Å
AuthorsEbenhoch, R. / Nar, H.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Immunohorizons / Year: 2023
Title: Anti-GARP Antibodies Inhibit Release of TGF-β by Regulatory T Cells via Different Modes of Action, but Do Not Influence Their Function In Vitro.
Authors: Frederik H Igney / Rebecca Ebenhoch / Felix Schiele / Herbert Nar /
Abstract: Regulatory T cells (Treg) play a critical role in controlling immune responses in diseases such as cancer or autoimmunity. Activated Treg express the membrane protein GARP (LRRC32) in complex with ...Regulatory T cells (Treg) play a critical role in controlling immune responses in diseases such as cancer or autoimmunity. Activated Treg express the membrane protein GARP (LRRC32) in complex with the latent form of the immunosuppressive cytokine TGF-β (L-TGF-β). In this study, we confirmed that active TGF-β was generated from its latent form in an integrin-dependent manner and induced TGF-β receptor signaling in activated human Treg. We studied a series of Abs targeting the L-TGF-β/GARP complex with distinct binding modes. We found that TGF-β receptor signaling could be inhibited by anti-TGF-β and by some, but not all, Abs against the L-TGF-β/GARP complex. Cryogenic electron microscopy structures of three L-TGF-β/GARP complex-targeting Abs revealed their distinct epitopes and allowed us to elucidate how they achieve blockade of TGF-β activation. Three different modes of action were identified, including a novel unusual mechanism of a GARP-binding Ab. However, blockade of GARP or TGF-β by Abs did not influence the suppressive activity of human Treg in vitro. We were also not able to confirm a prominent role of GARP in other functions of human Treg, such as FOXP3 induction and Treg stability. These data show that the GARP/TGF-β axis can be targeted pharmacologically in different ways, but further studies are necessary to understand its complexity and to unleash its therapeutic potential.
History
DepositionJan 16, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Mar 1, 2023Provider: repository / Type: Initial release
Revision 1.0Mar 1, 2023Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Mar 1, 2023Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Mar 1, 2023Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Mar 1, 2023Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Mar 1, 2023Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.0Mar 1, 2023Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Mar 1, 2023Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Mar 1, 2023Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Mar 1, 2023Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.0Mar 1, 2023Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Mar 1, 2023Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Mar 1, 2023Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Mar 1, 2023Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.0Mar 1, 2023Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Mar 1, 2023Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Mar 1, 2023Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Mar 1, 2023Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.1Mar 29, 2023Group: Database references / Category: citation / citation_author
Item: _citation.journal_abbrev / _citation.journal_id_CSD ..._citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.identifier_ORCID / _citation_author.name
Revision 1.2Oct 9, 2024Group: Data collection / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / em_admin / pdbx_entry_details / pdbx_modification_feature
Item: _em_admin.last_update / _pdbx_entry_details.has_protein_modification
Revision 1.3Nov 6, 2024Group: Data collection / Structure summary / Category: em_admin / struct
Item: _em_admin.last_update / _em_admin.title / _struct.title
Revision 1.4Jul 9, 2025Group: Data collection / Category: em_admin / em_software / Item: _em_admin.last_update / _em_software.name
Revision 1.1Jul 9, 2025Data content type: EM metadata / Data content type: EM metadata / EM metadata / Group: Data processing / Experimental summary / Data content type: EM metadata / EM metadata / Category: em_admin / em_software / Data content type: EM metadata / EM metadata / Item: _em_admin.last_update / _em_software.name

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Transforming growth factor beta-1
B: Transforming growth factor beta-1
C: Transforming growth factor beta-1
D: Transforming growth factor beta-1
I: Transforming growth factor beta activator LRRC32
L: 28G11 Fab heavy chain
K: 28G11 Fab light chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)197,42210
Polymers195,6627
Non-polymers1,7603
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area18620 Å2
ΔGint-68 kcal/mol
Surface area57000 Å2

-
Components

-
Transforming growth factor beta- ... , 2 types, 4 molecules ACBD

#1: Protein Transforming growth factor beta-1 / TGF-beta-1


Mass: 28531.488 Da / Num. of mol.: 2 / Fragment: LAP
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TGFB1, TGFB / Production host: Homo sapiens (human) / References: UniProt: P01137
#2: Protein Transforming growth factor beta-1 / TGF-beta-1


Mass: 12809.812 Da / Num. of mol.: 2 / Fragment: Mature
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TGFB1, TGFB / Production host: Homo sapiens (human) / References: UniProt: P01137

-
Antibody , 2 types, 2 molecules LK

#4: Antibody 28G11 Fab heavy chain


Mass: 24529.211 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human)
#5: Antibody 28G11 Fab light chain


Mass: 23091.578 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human)

-
Protein / Sugars , 2 types, 4 molecules I

#3: Protein Transforming growth factor beta activator LRRC32 / Garpin / Glycoprotein A repetitions predominant / GARP / Leucine-rich repeat-containing protein 32


Mass: 65358.488 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: LRRC32, D11S833E / Production host: Homo sapiens (human) / References: UniProt: Q14392
#6: Polysaccharide beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 586.542 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DManpb1-4DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/2,3,2/[a2122h-1b_1-5_2*NCC/3=O][a1122h-1b_1-5]/1-1-2/a4-b1_b4-c1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-Manp]{}}}LINUCSPDB-CARE

-
Details

Has ligand of interestN
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: latTGF-beta in complex with Fab 28G11 / Type: COMPLEX / Source: RECOMBINANT
Molecular weightExperimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human) / Strain: HEK293
Buffer solutionpH: 7.4
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3
VitrificationInstrument: LEICA EM GP / Cryogen name: ETHANE / Humidity: 80 % / Chamber temperature: 4 K

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2800 nm / Nominal defocus min: 800 nm
Image recordingElectron dose: 40 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

-
Processing

SoftwareName: PHENIX / Version: dev_4839: / Classification: refinement
EM softwareName: PHENIX / Category: model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 418886 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00411889
ELECTRON MICROSCOPYf_angle_d0.67916246
ELECTRON MICROSCOPYf_dihedral_angle_d4.4621750
ELECTRON MICROSCOPYf_chiral_restr0.0421944
ELECTRON MICROSCOPYf_plane_restr0.0092095

+
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