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Open data
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Basic information
Entry | Database: PDB / ID: 7y1r | ||||||
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Title | Human L-TGF-beta1 in complex with the anchor protein LRRC33 | ||||||
![]() | (Transforming growth factor ...) x 2 | ||||||
![]() | SIGNALING PROTEIN / NRROS / anchor protein | ||||||
Function / homology | ![]() : / sequestering of TGFbeta in extracellular matrix / 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 ...: / sequestering of TGFbeta in extracellular matrix / 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 / 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 / digestive tract development / negative regulation of interleukin-17 production / surfactant homeostasis / deubiquitinase activator activity / microglia development / 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 / 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 / muscle cell cellular homeostasis Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.01 Å | ||||||
![]() | Duan, Z. / Zhang, Z. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Specificity of TGF-β1 signal designated by LRRC33 and integrin αβ. Authors: Zelin Duan / Xuezhen Lin / Lixia Wang / Qiuxin Zhen / Yuefeng Jiang / Chuxin Chen / Jing Yang / Chia-Hsueh Lee / Yan Qin / Ying Li / Bo Zhao / Jianchuan Wang / Zhe Zhang / ![]() ![]() Abstract: Myeloid lineage cells present the latent form of transforming growth factor-β1 (L-TGF-β1) to the membrane using an anchor protein LRRC33. Integrin αβ activates extracellular L-TGF-β1 to trigger ...Myeloid lineage cells present the latent form of transforming growth factor-β1 (L-TGF-β1) to the membrane using an anchor protein LRRC33. Integrin αβ activates extracellular L-TGF-β1 to trigger the downstream signaling functions. However, the mechanism designating the specificity of TGF-β1 presentation and activation remains incompletely understood. Here, we report cryo-EM structures of human L-TGF-β1/LRRC33 and integrin αβ/L-TGF-β1 complexes. Combined with biochemical and cell-based analyses, we demonstrate that LRRC33 only presents L-TGF-β1 but not the -β2 or -β3 isoforms due to difference of key residues on the growth factor domains. Moreover, we reveal a 2:2 binding mode of integrin αβ and L-TGF-β1, which shows higher avidity and more efficient L-TGF-β1 activation than previously reported 1:2 binding mode. We also uncover that the disulfide-linked loop of the integrin subunit β determines its exquisite affinity to L-TGF-β1. Together, our findings provide important insights into the specificity of TGF-β1 signaling achieved by LRRC33 and integrin αβ. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 199.9 KB | Display | ![]() |
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PDB format | ![]() | 160 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.6 MB | Display | ![]() |
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Full document | ![]() | 1.6 MB | Display | |
Data in XML | ![]() | 41.6 KB | Display | |
Data in CIF | ![]() | 59.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 33571MC ![]() 7y1tC 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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1 |
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Components
-Transforming growth factor ... , 2 types, 3 molecules ABE
#1: Protein | Mass: 43010.402 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #2: Protein | | Mass: 72191.219 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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-Sugars , 4 types, 8 molecules ![](data/chem/img/NAG.gif)
#3: 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 Source method: isolated from a genetically manipulated source #4: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #5: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #6: Sugar | ChemComp-NAG / | |
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-Details
Has ligand of interest | Y |
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Sequence details | The first 16 residues of chain A, B, and E (MPLLLLLPLL |
-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: L-TGF-beta1 in complex with its anchor protein LRRC33 / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Molecular weight | Value: 0.15 MDa / Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: GOLD / Grid mesh size: 400 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
Vitrification | Cryogen name: ETHANE |
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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: 1200 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 60 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
EM software | Name: SerialEM / Category: image acquisition |
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CTF correction | Type: NONE |
3D reconstruction | Resolution: 4.01 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 254673 / Symmetry type: POINT |
Atomic model building | Protocol: OTHER |