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Yorodumi- PDB-7stk: Full-length insulin receptor bound with unsaturated insulin WT (2... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7stk | ||||||
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Title | Full-length insulin receptor bound with unsaturated insulin WT (2 insulins bound) asymmetric conformation (Conformation 2) | ||||||
Components |
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Keywords | SIGNALING PROTEIN / insulin receptor / site 1 binding deficient mutant insulin | ||||||
Function / homology | Function and homology information Signaling by Insulin receptor / Insulin receptor recycling / yolk / IRS activation / Insulin receptor signalling cascade / Signal attenuation / 3-phosphoinositide-dependent protein kinase binding / positive regulation of glycoprotein biosynthetic process / lipoic acid binding / regulation of hydrogen peroxide metabolic process ...Signaling by Insulin receptor / Insulin receptor recycling / yolk / IRS activation / Insulin receptor signalling cascade / Signal attenuation / 3-phosphoinositide-dependent protein kinase binding / positive regulation of glycoprotein biosynthetic process / lipoic acid binding / regulation of hydrogen peroxide metabolic process / regulation of female gonad development / positive regulation of meiotic cell cycle / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / 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 / nuclear lumen / positive regulation of protein-containing complex disassembly / cargo receptor activity / dendritic spine maintenance / PTB domain binding / insulin binding / negative regulation of NAD(P)H oxidase activity / neuronal cell body membrane / adrenal gland development / negative regulation of glycogen catabolic process / regulation of cellular amino acid metabolic process / Signaling by Insulin receptor / IRS activation / nitric oxide-cGMP-mediated signaling / Insulin processing / negative regulation of fatty acid metabolic process / negative regulation of feeding behavior / 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 / regulation of embryonic development / positive regulation of receptor internalization / negative regulation of acute inflammatory response / alpha-beta T cell activation / negative regulation of respiratory burst involved in inflammatory response / insulin receptor substrate binding / positive regulation of dendritic spine maintenance / Synthesis, secretion, and deacylation of Ghrelin / epidermis development / positive regulation of glycogen biosynthetic process / negative regulation of protein secretion / Signal attenuation / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / response to tumor necrosis factor / negative regulation of gluconeogenesis / positive regulation of nitric oxide mediated signal transduction / fatty acid homeostasis / regulation of protein localization to plasma membrane / phosphatidylinositol 3-kinase binding / COPI-mediated anterograde transport / negative regulation of lipid catabolic process / positive regulation of lipid biosynthetic process / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / heart morphogenesis / positive regulation of insulin receptor signaling pathway / positive regulation of phosphorylation / negative regulation of reactive oxygen species biosynthetic process / transport vesicle / positive regulation of protein autophosphorylation / dendrite membrane / Insulin receptor recycling / insulin-like growth factor receptor binding / NPAS4 regulates expression of target genes / positive regulation of protein metabolic process / neuron projection maintenance / positive regulation of brown fat cell differentiation / endoplasmic reticulum-Golgi intermediate compartment membrane / activation of protein kinase B activity / positive regulation of glycolytic process / response to nutrient levels / Insulin receptor signalling cascade / receptor-mediated endocytosis / positive regulation of mitotic nuclear division / negative regulation of protein phosphorylation / Regulation of insulin secretion / positive regulation of long-term synaptic potentiation / caveola / endosome lumen / positive regulation of cytokine production / acute-phase response / positive regulation of protein secretion / positive regulation of nitric-oxide synthase activity / regulation of transmembrane transporter activity / positive regulation of cell differentiation / positive regulation of glucose import / negative regulation of proteolysis / animal organ morphogenesis / regulation of synaptic plasticity Similarity search - Function | ||||||
Biological species | Mus musculus (house mouse) Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4 Å | ||||||
Authors | Bai, X.C. / Choi, E. | ||||||
Funding support | United States, 1items
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Citation | Journal: Nat Struct Mol Biol / Year: 2022 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: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7stk.cif.gz | 363.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7stk.ent.gz | 290.4 KB | Display | PDB format |
PDBx/mmJSON format | 7stk.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/st/7stk ftp://data.pdbj.org/pub/pdb/validation_reports/st/7stk | HTTPS FTP |
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-Related structure data
Related structure data | 25431MC 7sl1C 7sl2C 7sl3C 7sl4C 7sl6C 7sl7C 7sthC 7stiC 7stjC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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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.) Mus musculus (house mouse) / Gene: Insr / Production host: Homo sapiens (human) References: UniProt: P15208, receptor protein-tyrosine kinase #2: Protein | Mass: 11989.862 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: INS / Production host: Homo sapiens (human) / References: UniProt: P01308 |
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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 |
-Sample preparation
Component | Name: Full-length insulin receptor bound with unsaturated insulin WT (2 insulins bound) asymmetric conformation (Conformation 2) Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Mus musculus (house mouse) |
Source (recombinant) | Organism: Homo sapiens (human) |
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 % |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy / 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) |
-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 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 46052 / Symmetry type: POINT |