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- PDB-7sti: Full-length insulin receptor bound with unsaturated insulin WT (1... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7sti | ||||||
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Title | Full-length insulin receptor bound with unsaturated insulin WT (1 insulin bound) asymmetric conformation | ||||||
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![]() | SIGNALING PROTEIN / insulin receptor / site 1 binding deficient mutant insulin | ||||||
Function / homology | ![]() Signaling by Insulin receptor / yolk / IRS activation / Insulin receptor signalling cascade / Signal attenuation / Insulin receptor recycling / 3-phosphoinositide-dependent protein kinase binding / positive regulation of glycoprotein biosynthetic process / lipoic acid binding / regulation of female gonad development ...Signaling by Insulin receptor / yolk / IRS activation / Insulin receptor signalling cascade / Signal attenuation / Insulin receptor recycling / 3-phosphoinositide-dependent protein kinase binding / positive regulation of glycoprotein biosynthetic process / lipoic acid binding / regulation of female gonad development / regulation of hydrogen peroxide metabolic process / positive regulation of meiotic cell cycle / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / nuclear lumen / positive regulation of developmental growth / insulin-like growth factor II binding / male sex determination / exocrine pancreas development / insulin receptor complex / insulin-like growth factor I binding / insulin receptor activity / positive regulation of protein-containing complex disassembly / cargo receptor activity / dendritic spine maintenance / insulin binding / PTB domain binding / negative regulation of NAD(P)H oxidase activity / negative regulation of glycogen catabolic process / regulation of cellular amino acid metabolic process / adrenal gland development / negative regulation of fatty acid metabolic process / neuronal cell body membrane / negative regulation of feeding behavior / Signaling by Insulin receptor / IRS activation / Insulin processing / regulation of protein secretion / amyloid-beta clearance / positive regulation of peptide hormone secretion / positive regulation of respiratory burst / Regulation of gene expression in beta cells / nitric oxide-cGMP-mediated signaling / negative regulation of acute inflammatory response / positive regulation of receptor internalization / alpha-beta T cell activation / regulation of embryonic development / negative regulation of respiratory burst involved in inflammatory response / insulin receptor substrate binding / positive regulation of dendritic spine maintenance / positive regulation of glycogen biosynthetic process / Synthesis, secretion, and deacylation of Ghrelin / epidermis development / negative regulation of protein secretion / regulation of protein localization to plasma membrane / positive regulation of nitric oxide mediated signal transduction / fatty acid homeostasis / Signal attenuation / response to tumor necrosis factor / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / negative regulation of lipid catabolic process / negative regulation of gluconeogenesis / phosphatidylinositol 3-kinase binding / COPI-mediated anterograde transport / positive regulation of lipid biosynthetic process / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / heart morphogenesis / negative regulation of reactive oxygen species biosynthetic process / positive regulation of insulin receptor signaling pathway / positive regulation of phosphorylation / transport vesicle / positive regulation of protein autophosphorylation / dendrite membrane / Insulin receptor recycling / neuron projection maintenance / NPAS4 regulates expression of target genes / positive regulation of protein metabolic process / positive regulation of brown fat cell differentiation / positive regulation of glycolytic process / activation of protein kinase B activity / endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of mitotic nuclear division / Insulin receptor signalling cascade / response to nutrient levels / receptor-mediated endocytosis / negative regulation of protein phosphorylation / positive regulation of nitric-oxide synthase activity / positive regulation of cytokine production / positive regulation of long-term synaptic potentiation / Regulation of insulin secretion / caveola / acute-phase response / endosome lumen / positive regulation of protein secretion / positive regulation of glucose import / positive regulation of cell differentiation / negative regulation of proteolysis / regulation of transmembrane transporter activity / animal organ morphogenesis / insulin-like growth factor receptor binding / wound healing Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.9 Å | ||||||
![]() | Bai, X.C. / Choi, E. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Synergistic activation of the insulin receptor via two distinct sites. Authors: Jie Li / Junhee Park / John P Mayer / Kristofor J Webb / Emiko Uchikawa / Jiayi Wu / Shun Liu / Xuewu Zhang / Michael H B Stowell / Eunhee Choi / Xiao-Chen Bai / ![]() Abstract: Insulin receptor (IR) signaling controls multiple facets of animal physiology. Maximally four insulins bind to IR at two distinct sites, termed site-1 and site-2. However, the precise functional ...Insulin receptor (IR) signaling controls multiple facets of animal physiology. Maximally four insulins bind to IR at two distinct sites, termed site-1 and site-2. However, the precise functional roles of each binding event during IR activation remain unresolved. Here, we showed that IR incompletely saturated with insulin predominantly forms an asymmetric conformation and exhibits partial activation. IR with one insulin bound adopts a Γ-shaped conformation. IR with two insulins bound assumes a Ƭ-shaped conformation. One insulin binds at site-1 and another simultaneously contacts both site-1 and site-2 in the Ƭ-shaped IR dimer. We further show that concurrent binding of four insulins to sites-1 and -2 prevents the formation of asymmetric IR and promotes the T-shaped symmetric, fully active state. Collectively, our results demonstrate how the synergistic binding of multiple insulins promotes optimal IR activation. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 356.4 KB | Display | ![]() |
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PDB format | ![]() | 283 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 679.5 KB | Display | ![]() |
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Full document | ![]() | 731.9 KB | Display | |
Data in XML | ![]() | 54.4 KB | Display | |
Data in CIF | ![]() | 81.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 25429MC ![]() 7sl1C ![]() 7sl2C ![]() 7sl3C ![]() 7sl4C ![]() 7sl6C ![]() 7sl7C ![]() 7sthC ![]() 7stjC ![]() 7stkC C: citing same article ( M: map data used to model this data |
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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
#1: Protein | Mass: 155790.516 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: P15208, receptor protein-tyrosine kinase #2: Protein | | Mass: 11989.862 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
Component | Name: Full-length insulin receptor bound with unsaturated insulin WT (1 insulin bound) asymmetric conformation Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 8 |
Specimen | Conc.: 6 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
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 / Nominal defocus max: 2600 nm / Nominal defocus min: 1600 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 2030596 | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 6130 / Symmetry type: POINT |