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Yorodumi- EMDB-10311: Human insulin receptor ectodomain bound by several insulins in an... -
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-Basic information
Entry | Database: EMDB / ID: EMD-10311 | |||||||||||||||
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Title | Human insulin receptor ectodomain bound by several insulins in an intermediate state | |||||||||||||||
Map data | manually filtered, sharpened and masked map. In manuscript labeled as "intermediate state". On different origin as the other maps. | |||||||||||||||
Sample |
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Function / homology | Function and homology information regulation of female gonad development / positive regulation of meiotic cell cycle / 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 ...regulation of female gonad development / positive regulation of meiotic cell cycle / 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 / positive regulation of nitric oxide mediated signal transduction / negative regulation of fatty acid metabolic process / negative regulation of feeding behavior / neuronal cell body membrane / Signaling by Insulin receptor / IRS activation / activation of protein kinase activity / Insulin processing / regulation of protein secretion / amyloid-beta clearance / positive regulation of respiratory burst / positive regulation of peptide hormone secretion / Regulation of gene expression in beta cells / 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 / transport across blood-brain barrier / 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 / Signal attenuation / negative regulation of lipid catabolic process / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / negative regulation of gluconeogenesis / phosphatidylinositol 3-kinase binding / COPI-mediated anterograde transport / positive regulation of lipid biosynthetic process / heart morphogenesis / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / negative regulation of reactive oxygen species biosynthetic process / positive regulation of insulin receptor signaling pathway / nitric oxide-cGMP-mediated signaling / 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 / receptor-mediated endocytosis / learning / 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 / endosome lumen / positive regulation of protein secretion / positive regulation of glucose import / negative regulation of proteolysis / positive regulation of cell differentiation / regulation of transmembrane transporter activity / insulin-like growth factor receptor binding / positive regulation of MAP kinase activity / wound healing / insulin receptor binding / regulation of synaptic plasticity / negative regulation of protein catabolic process / hormone activity / receptor internalization / receptor protein-tyrosine kinase / memory / cognition / cellular response to growth factor stimulus / positive regulation of neuron projection development / positive regulation of protein localization to nucleus / Golgi lumen / peptidyl-tyrosine phosphorylation Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 5.0 Å | |||||||||||||||
Authors | Gutmann T / Schaefer IB / Poojari C / Brankatschk B / Vattulainen I / Strauss M / Coskun U | |||||||||||||||
Funding support | Germany, Finland, 4 items
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Citation | Journal: J Cell Biol / Year: 2020 Title: Cryo-EM structure of the complete and ligand-saturated insulin receptor ectodomain. Authors: Theresia Gutmann / Ingmar B Schäfer / Chetan Poojari / Beate Brankatschk / Ilpo Vattulainen / Mike Strauss / Ünal Coskun / Abstract: Glucose homeostasis and growth essentially depend on the hormone insulin engaging its receptor. Despite biochemical and structural advances, a fundamental contradiction has persisted in the current ...Glucose homeostasis and growth essentially depend on the hormone insulin engaging its receptor. Despite biochemical and structural advances, a fundamental contradiction has persisted in the current understanding of insulin ligand-receptor interactions. While biochemistry predicts two distinct insulin binding sites, 1 and 2, recent structural analyses have resolved only site 1. Using a combined approach of cryo-EM and atomistic molecular dynamics simulation, we present the structure of the entire dimeric insulin receptor ectodomain saturated with four insulin molecules. Complementing the previously described insulin-site 1 interaction, we present the first view of insulin bound to the discrete insulin receptor site 2. Insulin binding stabilizes the receptor ectodomain in a T-shaped conformation wherein the membrane-proximal domains converge and contact each other. These findings expand the current models of insulin binding to its receptor and of its regulation. In summary, we provide the structural basis for a comprehensive description of ligand-receptor interactions that ultimately will inform new approaches to structure-based drug design. #1: Journal: Biorxiv / Year: 2019 Title: Cryo-EM structure of the complete and ligand-saturated insulin receptor ectodomain Authors: Gutmann T / Schafer I / Poojari C / Brankatschk B / Vattulainen I / Strauss M / Coskun U | |||||||||||||||
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_10311.map.gz | 3.4 MB | EMDB map data format | |
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Header (meta data) | emd-10311-v30.xml emd-10311.xml | 20.7 KB 20.7 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_10311_fsc.xml | 10.3 KB | Display | FSC data file |
Images | emd_10311.png | 124.7 KB | ||
Masks | emd_10311_msk_1.map | 91.1 MB | Mask map | |
Others | emd_10311_additional.map.gz emd_10311_additional_1.map.gz emd_10311_half_map_1.map.gz emd_10311_half_map_2.map.gz | 5.4 MB 5.4 MB 71.3 MB 71.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-10311 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-10311 | HTTPS FTP |
-Validation report
Summary document | emd_10311_validation.pdf.gz | 362.9 KB | Display | EMDB validaton report |
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Full document | emd_10311_full_validation.pdf.gz | 362 KB | Display | |
Data in XML | emd_10311_validation.xml.gz | 16.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-10311 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-10311 | HTTPS FTP |
-Related structure data
Related structure data | 7qidMUC 6sofC C: citing same article (ref.) M: atomic model generated by this map U: unfit; in different coordinate system*YM |
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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_10311.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | manually filtered, sharpened and masked map. In manuscript labeled as "intermediate state". On different origin as the other maps. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.06 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_10311_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: automatically filtered, sharpened and masked map. In manuscript...
File | emd_10311_additional.map | ||||||||||||
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Annotation | automatically filtered, sharpened and masked map. In manuscript labeled as "intermediate state". | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: automatically filtered, sharpened and masked map. In manuscript...
File | emd_10311_additional_1.map | ||||||||||||
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Annotation | automatically filtered, sharpened and masked map. In manuscript labeled as "intermediate state". | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half-map 1 used as input for postprocessing to...
File | emd_10311_half_map_1.map | ||||||||||||
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Annotation | half-map 1 used as input for postprocessing to generate the main map (post Bayesian polishing and 3D refinement) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half-map 2 used as input for postprocessing to...
File | emd_10311_half_map_2.map | ||||||||||||
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Annotation | half-map 2 used as input for postprocessing to generate the main map (post Bayesian polishing and 3D refinement) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : human insulin receptor ectodomain bound by several insulins in an...
Entire | Name: human insulin receptor ectodomain bound by several insulins in an intermediate state |
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Components |
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-Supramolecule #1: human insulin receptor ectodomain bound by several insulins in an...
Supramolecule | Name: human insulin receptor ectodomain bound by several insulins in an intermediate state type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
Molecular weight | Experimental: 375 KDa |
-Macromolecule #1: human insulin receptor ectodomain
Macromolecule | Name: human insulin receptor ectodomain / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: HLYPGEVCPG MDIRNNLTRL HELENCSVIE GHLQILLMFK TRPEDFRDLS FPKLIMITDY LLLFRVYGLE SLKDLFPNL TVIRGSRLFF NYALVIFEMV HLKELGLYNL MNITRGSVRI EKNNELCYLA TIDWSRILDS V EDNYIVLN KDDNEECGDI CPGTAKGKTN ...String: HLYPGEVCPG MDIRNNLTRL HELENCSVIE GHLQILLMFK TRPEDFRDLS FPKLIMITDY LLLFRVYGLE SLKDLFPNL TVIRGSRLFF NYALVIFEMV HLKELGLYNL MNITRGSVRI EKNNELCYLA TIDWSRILDS V EDNYIVLN KDDNEECGDI CPGTAKGKTN CPATVINGQF VERCWTHSHC QKVCPTICKS HGCTAEGLCC HS ECLGNCS QPDDPTKCVA CRNFYLDGRC VETCPPPYYH FQDWRCVNFS FCQDLHHKCK NSRRQGCHQY VIH NNKCIP ECPSGYTMNS SNLLCTPCLG PCPKVCHLLE GEKTIDSVTS AQELRGCTVI NGSLIINIRG GNNL AAELE ANLGLIEEIS GYLKIRRSYA LVSLSFFRKL RLIRGETLEI GNYSFYALDN QNLRQLWDWS KHNLT ITQG KLFFHYNPKL CLSEIHKMEE VSGTKGRQER NDIALKTNGD QASCENELLK FSYIRTSFDK ILLRWE PYW PPDFRDLLGF MLFYKEAPYQ NVTEFDGQDA CGSNSWTVVD IDPPLRSNDP KSQNHPGWLM RGLKPWT QY AIFVKTLVTF SDERRTYGAK SDIIYVQTDA TNPSVPLDPI SVSNSSSQII LKWKPPSDPN GNITHYLV F WERQAEDSEL FELDYCLKGL KLPSRTWSPP FESEDSQKHN QSEYEDSAGE CCSCPKTDSQ ILKELEESS FRKTFEDYLH NVVFVPRPS HRPFEKVVNK ESLVISGLRH FTGYRIELQA CNQDTPEERC SVAAYVSART MPEAKADDIV GPVTHEIFEN NVVHLMWQE PKEPNGLIVL YEVSYRRYGD EELHLCVSRK HFALERGCRL RGLSPGNYSV RIRATSLAGN G SWTEPTYF YVTDYLDVPS NIAK |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE-PROPANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Number grids imaged: 1 / Number real images: 51 / Average exposure time: 10.2 sec. / Average electron dose: 55.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |