[English] 日本語
Yorodumi- PDB-7y1t: Complex of integrin alphaV/beta8 and L-TGF-beta1 at a ratio of 1:2 -
+Open data
-Basic information
Entry | Database: PDB / ID: 7y1t | ||||||
---|---|---|---|---|---|---|---|
Title | Complex of integrin alphaV/beta8 and L-TGF-beta1 at a ratio of 1:2 | ||||||
Components |
| ||||||
Keywords | SIGNALING PROTEIN | ||||||
Function / homology | Function and homology information ganglioside metabolic process / 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 / positive regulation of primary miRNA processing / 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 ...ganglioside metabolic process / 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 / positive regulation of primary miRNA processing / 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 / integrin alphav-beta6 complex / integrin alphav-beta8 complex / hard palate development / transforming growth factor beta production / negative regulation of macrophage cytokine production / negative regulation of entry of bacterium into host cell / integrin alphav-beta5 complex / odontoblast differentiation / opsonin binding / 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 / integrin alphav-beta1 complex / mammary gland branching involved in thelarche / SMAD2/3 Phosphorylation Motif Mutants in Cancer / TGFBR1 KD Mutants in Cancer / Cross-presentation of particulate exogenous antigens (phagosomes) / retina vasculature development in camera-type eye / heart valve morphogenesis / extracellular matrix protein binding / macrophage derived foam cell differentiation / membrane protein intracellular domain proteolysis / response to laminar fluid shear stress / positive regulation of vasculature development / bronchiole development / hyaluronan catabolic process / ATP biosynthetic process / Laminin interactions / positive regulation of branching involved in ureteric bud morphogenesis / positive regulation of extracellular matrix assembly / receptor catabolic process / placenta blood vessel development / lens fiber cell differentiation / negative regulation of extracellular matrix disassembly / integrin alphav-beta3 complex / negative regulation of lipoprotein metabolic process / type II transforming growth factor beta receptor binding / oligodendrocyte development / TGFBR1 LBD Mutants in Cancer / alphav-beta3 integrin-PKCalpha complex / entry into host cell by a symbiont-containing vacuole / response to salt / germ cell migration / negative regulation of biomineral tissue development / positive regulation of mononuclear cell migration / alphav-beta3 integrin-HMGB1 complex / endoderm development / type I transforming growth factor beta receptor binding / phospholipid homeostasis / positive regulation of chemotaxis / negative regulation of lipid transport / negative regulation of myoblast differentiation / positive regulation of endothelial cell apoptotic process / positive regulation of vascular permeability / negative regulation of low-density lipoprotein receptor activity / cell-cell junction organization / regulation of phagocytosis / response to vitamin D / Elastic fibre formation / positive regulation of regulatory T cell differentiation / alphav-beta3 integrin-IGF-1-IGF1R complex / transforming growth factor beta binding / response to cholesterol / digestive tract development / negative regulation of interleukin-17 production / surfactant homeostasis / deubiquitinase activator activity / negative regulation of release of sequestered calcium ion into cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.24 Å | ||||||
Authors | Duan, Z. / Zhang, Z. | ||||||
Funding support | China, 1items
| ||||||
Citation | Journal: Nat Commun / Year: 2022 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 |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 7y1t.cif.gz | 202 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb7y1t.ent.gz | 155.5 KB | Display | PDB format |
PDBx/mmJSON format | 7y1t.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/y1/7y1t ftp://data.pdbj.org/pub/pdb/validation_reports/y1/7y1t | HTTPS FTP |
---|
-Related structure data
Related structure data | 33572MC 7y1rC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
-Protein , 3 types, 3 molecules ABD
#1: Protein | Mass: 69812.711 Da / Num. of mol.: 1 / Mutation: M401C Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ITGAV / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P06756 |
---|---|
#2: Protein | Mass: 53017.355 Da / Num. of mol.: 1 / Mutation: V259C Source method: isolated from a genetically manipulated source Details: The first 21 residues (MDMRVPAQLLGLLLLWFSGVL) are signal peptides. Source: (gene. exp.) Homo sapiens (human) / Gene: ITGB8 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P26012 |
#3: Protein | Mass: 43010.402 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: The first 16 residues (MPLLLLLPLLWAGALA) are signal peptides. Source: (gene. exp.) Homo sapiens (human) / Gene: TGFB1, TGFB / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P01137 |
-Sugars , 4 types, 9 molecules
#4: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2- ...2-acetamido-2-deoxy-beta-D-glucopyranose-(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 | ||||
---|---|---|---|---|---|
#5: Polysaccharide | Source method: isolated from a genetically manipulated source #6: Polysaccharide | alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-4)-[alpha-D-mannopyranose-(1-3)]beta-D- ...alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-4)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Type: oligosaccharide / Mass: 1072.964 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source #7: Sugar | ChemComp-NAG / |
-Non-polymers , 2 types, 6 molecules
#8: Chemical | ChemComp-CA / #9: Chemical | ChemComp-MN / | |
---|
-Details
Has ligand of interest | Y |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Complex of integrin alphaV/beta8 and L-TGF-beta1 at a ratio of 1:2 Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT |
---|---|
Molecular weight | Value: 0.21 MDa / Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) / Cell: HEK293 |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
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) |
-Processing
EM software | Name: SerialEM / Category: image acquisition |
---|---|
CTF correction | Type: NONE |
3D reconstruction | Resolution: 3.24 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 305011 / Symmetry type: POINT |
Atomic model building | Protocol: OTHER |