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Yorodumi- EMDB-7463: Insulin Receptor ectodomain in complex with two insulin molecules... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-7463 | ||||||||||||
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Title | Insulin Receptor ectodomain in complex with two insulin molecules - C1 symmetry | ||||||||||||
Map data | Receptor ectodomain in complex with two insulin molecules - C1 symmetry | ||||||||||||
Sample |
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Function / homology | Function and homology information cellular response to palmitoleic acid / response to L-arginine / regulation of female gonad development / positive regulation of meiotic cell cycle / 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 ...cellular response to palmitoleic acid / response to L-arginine / regulation of female gonad development / positive regulation of meiotic cell cycle / 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 / activation of protein kinase activity / 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 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 / transport across blood-brain barrier / 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 / 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 / receptor-mediated endocytosis / positive regulation of MAP kinase activity / positive regulation of nitric-oxide synthase activity / learning / 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 / regulation of transmembrane transporter activity / insulin receptor binding / wound healing / peptidyl-tyrosine phosphorylation / regulation of synaptic plasticity / vasodilation / hormone activity / cellular response to insulin stimulus / receptor internalization / memory / cognition Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) / Ovis aries (sheep) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.7 Å | ||||||||||||
Authors | Scapin G / Dandey VP / Zhang Z / Strickland C / Potter CS / Carragher B | ||||||||||||
Funding support | United States, 3 items
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Citation | Journal: Nature / Year: 2018 Title: Structure of the insulin receptor-insulin complex by single-particle cryo-EM analysis. Authors: Giovanna Scapin / Venkata P Dandey / Zhening Zhang / Winifred Prosise / Alan Hruza / Theresa Kelly / Todd Mayhood / Corey Strickland / Clinton S Potter / Bridget Carragher / Abstract: The insulin receptor is a dimeric protein that has a crucial role in controlling glucose homeostasis, regulating lipid, protein and carbohydrate metabolism, and modulating brain neurotransmitter ...The insulin receptor is a dimeric protein that has a crucial role in controlling glucose homeostasis, regulating lipid, protein and carbohydrate metabolism, and modulating brain neurotransmitter levels. Insulin receptor dysfunction has been associated with many diseases, including diabetes, cancer and Alzheimer's disease. The primary sequence of the receptor has been known since the 1980s, and is composed of an extracellular portion (the ectodomain, ECD), a single transmembrane helix and an intracellular tyrosine kinase domain. Binding of insulin to the dimeric ECD triggers auto-phosphorylation of the tyrosine kinase domain and subsequent activation of downstream signalling molecules. Biochemical and mutagenesis data have identified two putative insulin-binding sites, S1 and S2. The structures of insulin bound to an ECD fragment containing S1 and of the apo ectodomain have previously been reported, but details of insulin binding to the full receptor and the signal propagation mechanism are still not understood. Here we report single-particle cryo-electron microscopy reconstructions of the 1:2 (4.3 Å) and 1:1 (7.4 Å) complexes of the insulin receptor ECD dimer with insulin. The symmetrical 4.3 Å structure shows two insulin molecules per dimer, each bound between the leucine-rich subdomain L1 of one monomer and the first fibronectin-like domain (FnIII-1) of the other monomer, and making extensive interactions with the α-subunit C-terminal helix (α-CT helix). The 7.4 Å structure has only one similarly bound insulin per receptor dimer. The structures confirm the binding interactions at S1 and define the full S2 binding site. These insulin receptor states suggest that recruitment of the α-CT helix upon binding of the first insulin changes the relative subdomain orientations and triggers downstream signal propagation. | ||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_7463.map.gz | 85.5 MB | EMDB map data format | |
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Header (meta data) | emd-7463-v30.xml emd-7463.xml | 18.3 KB 18.3 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_7463_fsc.xml | 12 KB | Display | FSC data file |
Images | emd_7463.png | 74.7 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-7463 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-7463 | HTTPS FTP |
-Validation report
Summary document | emd_7463_validation.pdf.gz | 429.7 KB | Display | EMDB validaton report |
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Full document | emd_7463_full_validation.pdf.gz | 429.3 KB | Display | |
Data in XML | emd_7463_validation.xml.gz | 11.7 KB | Display | |
Data in CIF | emd_7463_validation.cif.gz | 15.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-7463 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-7463 | HTTPS FTP |
-Related structure data
Related structure data | 6cebMC 7461C 7462C 6ce7C 6ce9C C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_7463.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Receptor ectodomain in complex with two insulin molecules - C1 symmetry | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
+Entire : Insulin Receptor Ectodomain in complex with two insulin molecules...
+Supramolecule #1: Insulin Receptor Ectodomain in complex with two insulin molecules...
+Supramolecule #2: Insulin receptor
+Supramolecule #3: Insulin receptor subunit alpha
+Supramolecule #4: Insulin A chain
+Supramolecule #5: Insulin B chain
+Macromolecule #1: Insulin receptor
+Macromolecule #2: Insulin receptor
+Macromolecule #3: Insulin A chain
+Macromolecule #4: Insulin B chain
+Macromolecule #9: 2-acetamido-2-deoxy-beta-D-glucopyranose
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.3 mg/mL |
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Buffer | pH: 7.5 / Details: Hepes Saline (HBS) |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 80 % / Chamber temperature: 293 K / Instrument: HOMEMADE PLUNGER / Details: Grids made with SpotItOn. |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Detector mode: COUNTING / Average electron dose: 45.5 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Protocol: RIGID BODY FIT |
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Output model | PDB-6ceb: |