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- PDB-6pyh: Cryo-EM structure of full-length IGF1R-IGF1 complex. Only the ext... -
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Basic information
Entry | Database: PDB / ID: 6pyh | ||||||
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Title | Cryo-EM structure of full-length IGF1R-IGF1 complex. Only the extracellular region of the complex is resolved. | ||||||
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![]() | SIGNALING PROTEIN/HORMONE / IGF1R / IGF1 / SIGNALING PROTEIN-HORMONE complex | ||||||
Function / homology | ![]() Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / mitotic nuclear division / IRS-related events triggered by IGF1R / SHC-related events triggered by IGF1R / glycolate metabolic process / muscle hypertrophy / negative regulation of oocyte development / positive regulation of trophectodermal cell proliferation / insulin-like growth factor binding protein complex / insulin-like growth factor ternary complex ...Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / mitotic nuclear division / IRS-related events triggered by IGF1R / SHC-related events triggered by IGF1R / glycolate metabolic process / muscle hypertrophy / negative regulation of oocyte development / positive regulation of trophectodermal cell proliferation / insulin-like growth factor binding protein complex / insulin-like growth factor ternary complex / : / proteoglycan biosynthetic process / negative regulation of cholangiocyte apoptotic process / positive regulation of glycoprotein biosynthetic process / myotube cell development / Extra-nuclear estrogen signaling / skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration / insulin-like growth factor receptor activity / positive regulation of steroid hormone biosynthetic process / negative regulation of neuroinflammatory response / protein kinase complex / bone mineralization involved in bone maturation / Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / positive regulation of cell growth involved in cardiac muscle cell development / negative regulation of vascular associated smooth muscle cell apoptotic process / protein transporter activity / IRS-related events triggered by IGF1R / insulin-like growth factor binding / exocytic vesicle / negative regulation of muscle cell apoptotic process / positive regulation of meiotic cell cycle / positive regulation of DNA metabolic process / positive regulation of developmental growth / cell activation / positive regulation of calcineurin-NFAT signaling cascade / male sex determination / prostate gland epithelium morphogenesis / exocrine pancreas development / mammary gland development / insulin receptor complex / negative regulation of hepatocyte apoptotic process / positive regulation of transcription regulatory region DNA binding / insulin-like growth factor I binding / insulin receptor activity / transcytosis / alphav-beta3 integrin-IGF-1-IGF1R complex / positive regulation of kinase activity / positive regulation of Ras protein signal transduction / positive regulation of protein-containing complex disassembly / myoblast differentiation / positive regulation of insulin-like growth factor receptor signaling pathway / myoblast proliferation / muscle organ development / negative regulation of interleukin-1 beta production / dendritic spine maintenance / cellular response to insulin-like growth factor stimulus / response to L-glutamate / insulin binding / negative regulation of MAPK cascade / adrenal gland development / establishment of cell polarity / postsynaptic modulation of chemical synaptic transmission / protein tyrosine kinase activator activity / positive regulation of cardiac muscle hypertrophy / positive regulation of activated T cell proliferation / positive regulation of smooth muscle cell migration / positive regulation of axon regeneration / amyloid-beta clearance / negative regulation of release of cytochrome c from mitochondria / positive regulation of osteoblast proliferation / positive regulation of cytokinesis / negative regulation of amyloid-beta formation / negative regulation of smooth muscle cell apoptotic process / phosphatidylinositol-mediated signaling / regulation of JNK cascade / negative regulation of tumor necrosis factor production / insulin receptor substrate binding / estrous cycle / positive regulation of glycogen biosynthetic process / G-protein alpha-subunit binding / Synthesis, secretion, and deacylation of Ghrelin / epidermis development / epithelial to mesenchymal transition / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of DNA binding / SHC-related events triggered by IGF1R / positive regulation of osteoblast differentiation / phosphatidylinositol 3-kinase binding / peptidyl-tyrosine autophosphorylation / positive regulation of tyrosine phosphorylation of STAT protein / positive regulation of vascular associated smooth muscle cell proliferation / cellular response to transforming growth factor beta stimulus / cell surface receptor protein tyrosine kinase signaling pathway / T-tubule / positive regulation of glycolytic process / activation of protein kinase B activity / transmembrane receptor protein tyrosine kinase activity / protein serine/threonine kinase activator activity / positive regulation of mitotic nuclear division / cerebellum development Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.3 Å | ||||||
![]() | Li, J. / Choi, E. / Yu, H.T. / Bai, X.C. | ||||||
![]() | ![]() Title: Structural basis of the activation of type 1 insulin-like growth factor receptor. Authors: Jie Li / Eunhee Choi / Hongtao Yu / Xiao-Chen Bai / ![]() Abstract: Type 1 insulin-like growth factor receptor (IGF1R) is a receptor tyrosine kinase that regulates cell growth and proliferation, and can be activated by IGF1, IGF2, and insulin. Here, we report the ...Type 1 insulin-like growth factor receptor (IGF1R) is a receptor tyrosine kinase that regulates cell growth and proliferation, and can be activated by IGF1, IGF2, and insulin. Here, we report the cryo-EM structure of full-length IGF1R-IGF1 complex in the active state. This structure reveals that only one IGF1 molecule binds the Γ-shaped asymmetric IGF1R dimer. The IGF1-binding site is formed by the L1 and CR domains of one IGF1R protomer and the α-CT and FnIII-1 domains of the other. The liganded α-CT forms a rigid beam-like structure with the unliganded α-CT, which hinders the conformational change of the unliganded α-CT required for binding of a second IGF1 molecule. We further identify an L1-FnIII-2 interaction that mediates the dimerization of membrane-proximal domains of IGF1R. This interaction is required for optimal receptor activation. Our study identifies a source of the negative cooperativity in IGF1 binding to IGF1R and reveals the structural basis of IGF1R activation. | ||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 310.7 KB | Display | ![]() |
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PDB format | ![]() | 250.7 KB | Display | ![]() |
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-Validation report
Summary document | ![]() | 807.6 KB | Display | ![]() |
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Full document | ![]() | 865.9 KB | Display | |
Data in XML | ![]() | 55.6 KB | Display | |
Data in CIF | ![]() | 82.3 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 20524MC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 145279.906 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: Q60751, receptor protein-tyrosine kinase #2: Protein | | Mass: 7663.752 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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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
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Molecular weight | Value: 0.336 MDa / Experimental value: NO | ||||||||||||||||||||||||
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||
Specimen | Conc.: 7 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Specimen support | Details: unspecified | ||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % |
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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 / Cs: 2.7 mm / C2 aperture diameter: 70 µm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 15 sec. / Electron dose: 50 e/Å2 / Film or detector model: GATAN K2 IS (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.16_3549: / Classification: refinement | |||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 1431211 | |||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | |||||||||||||||||||||||||||
3D reconstruction | Resolution: 4.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 51573 / Symmetry type: POINT | |||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | |||||||||||||||||||||||||||
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