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Open data
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Basic information
Entry | Database: PDB / ID: 8c7h | ||||||
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Title | Cryo-EM Map of the latTGF-beta 28G11 Fab complex | ||||||
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![]() | IMMUNE SYSTEM / Fab-complex / GARP / lat-TGF-beta | ||||||
Function / homology | ![]() : / adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains / regulation of interleukin-23 production / branch elongation involved in mammary gland duct branching / regulation of branching involved in mammary gland duct morphogenesis / positive regulation of microglia differentiation / Influenza Virus Induced Apoptosis / frontal suture morphogenesis / negative regulation of skeletal muscle tissue development / regulation of enamel mineralization ...: / adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains / regulation of interleukin-23 production / branch elongation involved in mammary gland duct branching / regulation of branching involved in mammary gland duct morphogenesis / positive regulation of microglia differentiation / Influenza Virus Induced Apoptosis / frontal suture morphogenesis / negative regulation of skeletal muscle tissue development / regulation of enamel mineralization / regulatory T cell differentiation / regulation of cartilage development / TGFBR2 MSI Frameshift Mutants in Cancer / regulation of blood vessel remodeling / tolerance induction to self antigen / regulation of striated muscle tissue development / negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target / regulation of protein import into nucleus / embryonic liver development / columnar/cuboidal epithelial cell maturation / type III transforming growth factor beta receptor binding / positive regulation of odontogenesis / Langerhans cell differentiation / negative regulation of hyaluronan biosynthetic process / positive regulation of cardiac muscle cell differentiation / myofibroblast differentiation / positive regulation of receptor signaling pathway via STAT / connective tissue replacement involved in inflammatory response wound healing / positive regulation of exit from mitosis / extracellular matrix assembly / negative regulation of macrophage cytokine production / odontoblast differentiation / : / TGFBR2 Kinase Domain Mutants in Cancer / positive regulation of smooth muscle cell differentiation / positive regulation of isotype switching to IgA isotypes / secondary palate development / positive regulation of mesenchymal stem cell proliferation / mammary gland branching involved in thelarche / SMAD2/3 Phosphorylation Motif Mutants in Cancer / TGFBR1 KD Mutants in Cancer / membrane protein intracellular domain proteolysis / heart valve morphogenesis / retina vasculature development in camera-type eye / response to laminar fluid shear stress / positive regulation of primary miRNA processing / positive regulation of vasculature development / bronchiole development / hyaluronan catabolic process / regulation of transforming growth factor beta receptor signaling pathway / ATP biosynthetic process / receptor catabolic process / positive regulation of branching involved in ureteric bud morphogenesis / positive regulation of extracellular matrix assembly / lens fiber cell differentiation / negative regulation of extracellular matrix disassembly / type II transforming growth factor beta receptor binding / TGFBR1 LBD Mutants in Cancer / oligodendrocyte development / germ cell migration / response to salt / negative regulation of biomineral tissue development / endoderm development / type I transforming growth factor beta receptor binding / positive regulation of chemotaxis / phospholipid homeostasis / positive regulation of mononuclear cell migration / negative regulation of myoblast differentiation / positive regulation of endothelial cell apoptotic process / positive regulation of vascular permeability / response to vitamin D / cell-cell junction organization / positive regulation of regulatory T cell differentiation / transforming growth factor beta binding / response to cholesterol / negative regulation of interleukin-17 production / digestive tract development / surfactant homeostasis / deubiquitinase activator activity / 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 / positive regulation of fibroblast migration / aortic valve morphogenesis / phosphate-containing compound metabolic process / negative regulation of protein localization to plasma membrane / negative regulation of phagocytosis / sprouting angiogenesis / face morphogenesis / neural tube development / Molecules associated with elastic fibres / RUNX3 regulates CDKN1A transcription / negative regulation of cytokine production / ventricular cardiac muscle tissue morphogenesis / cellular response to insulin-like growth factor stimulus / ureteric bud development / positive regulation of epidermal growth factor receptor signaling pathway / macrophage derived foam cell differentiation / negative regulation of neuroblast proliferation / Syndecan interactions Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.7 Å | ||||||
![]() | Ebenhoch, R. / Nar, H. | ||||||
Funding support | 1items
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![]() | ![]() 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 |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 249.2 KB | Display | ![]() |
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PDB format | ![]() | 192.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.1 MB | Display | ![]() |
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Full document | ![]() | 1.1 MB | Display | |
Data in XML | ![]() | 43 KB | Display | |
Data in CIF | ![]() | 63.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 16460MC M: map data used to model this data C: citing same article ( |
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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
-Transforming growth factor beta- ... , 2 types, 4 molecules ACBD
#1: Protein | Mass: 28531.488 Da / Num. of mol.: 2 / Fragment: LAP Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #2: Protein | Mass: 12809.812 Da / Num. of mol.: 2 / Fragment: Mature Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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-Antibody , 2 types, 2 molecules LK
#4: Antibody | Mass: 24529.211 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#5: Antibody | Mass: 23091.578 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Protein / Sugars , 2 types, 4 molecules I
#3: Protein | Mass: 65358.488 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#6: Polysaccharide | Source method: isolated from a genetically manipulated source |
-Details
Has ligand of interest | N |
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-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
Component | Name: latTGF-beta in complex with Fab 28G11 / Type: COMPLEX / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.4 |
Specimen | 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: Quantifoil R1.2/1.3 |
Vitrification | Instrument: LEICA EM GP / Cryogen name: ETHANE / Humidity: 80 % / Chamber temperature: 4 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2800 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
Software | Name: PHENIX / Version: dev_4839: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 418886 / Symmetry type: POINT | ||||||||||||||||||||||||
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