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Yorodumi- PDB-7sti: Full-length insulin receptor bound with unsaturated insulin WT (1... -
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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 | ||||||
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 / 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 / insulin-like growth factor II binding / positive regulation of developmental growth / 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 / adrenal gland development / positive regulation of nitric oxide mediated signal transduction / negative regulation of fatty acid metabolic process / negative regulation of feeding behavior / Signaling by Insulin receptor / IRS activation / Insulin processing / neuronal cell body membrane / regulation of protein secretion / amyloid-beta clearance / positive regulation of peptide hormone secretion / positive regulation of respiratory burst / negative regulation of acute inflammatory response / Regulation of gene expression in beta cells / positive regulation of phosphorylation / positive regulation of receptor internalization / alpha-beta T cell activation / regulation of embryonic development / regulation of cellular amino acid metabolic process / 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 / fatty acid homeostasis / response to tumor necrosis factor / Signal attenuation / negative regulation of lipid catabolic process / negative regulation of gluconeogenesis / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / phosphatidylinositol 3-kinase binding / COPI-mediated anterograde transport / positive regulation of lipid biosynthetic process / heart morphogenesis / negative regulation of reactive oxygen species biosynthetic process / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / positive regulation of insulin receptor signaling pathway / nitric oxide-cGMP-mediated signaling / transport vesicle / positive regulation of protein autophosphorylation / Insulin receptor recycling / insulin-like growth factor receptor binding / dendrite membrane / neuron projection maintenance / NPAS4 regulates expression of target genes / positive regulation of protein metabolic process / positive regulation of brown fat cell differentiation / activation of protein kinase B activity / endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of glycolytic process / 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 / caveola / acute-phase response / Regulation of insulin secretion / negative regulation of protein catabolic process / endosome lumen / positive regulation of glucose import / positive regulation of protein secretion / receptor protein-tyrosine kinase / negative regulation of proteolysis / positive regulation of cell differentiation / animal organ morphogenesis Similarity search - Function | ||||||
Biological species | Mus musculus (house mouse) Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.9 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 | 7sti.cif.gz | 356.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7sti.ent.gz | 283 KB | Display | PDB format |
PDBx/mmJSON format | 7sti.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7sti_validation.pdf.gz | 679.5 KB | Display | wwPDB validaton report |
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Full document | 7sti_full_validation.pdf.gz | 731.9 KB | Display | |
Data in XML | 7sti_validation.xml.gz | 54.4 KB | Display | |
Data in CIF | 7sti_validation.cif.gz | 81.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/st/7sti ftp://data.pdbj.org/pub/pdb/validation_reports/st/7sti | HTTPS FTP |
-Related structure data
Related structure data | 25429MC 7sl1C 7sl2C 7sl3C 7sl4C 7sl6C 7sl7C 7sthC 7stjC 7stkC 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.: 1 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 (1 insulin bound) asymmetric conformation 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 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) |
-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 |