[English] 日本語
Yorodumi- EMDB-7461: Insulin Receptor ectodomain in complex with one insulin molecule -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-7461 | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Insulin Receptor ectodomain in complex with one insulin molecule | ||||||||||||
Map data | Insulin receptor dimer with one insulin bound | ||||||||||||
Sample |
| ||||||||||||
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 / 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 ...cellular response to palmitoleic acid / response to L-arginine / 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 / 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 / negative regulation of fatty acid metabolic process / Insulin processing / negative regulation of feeding behavior / regulation of protein secretion / amyloid-beta clearance / positive regulation of peptide hormone secretion / activation of protein kinase activity / Regulation of gene expression in beta cells / positive regulation of respiratory burst / regulation of embryonic development / positive regulation of receptor internalization / transport across blood-brain barrier / positive regulation of dendritic spine maintenance / alpha-beta T cell activation / negative regulation of acute inflammatory response / negative regulation of respiratory burst involved in inflammatory response / insulin receptor substrate binding / negative regulation of protein secretion / fatty acid homeostasis / Synthesis, secretion, and deacylation of Ghrelin / epidermis development / positive regulation of glycogen biosynthetic process / positive regulation of lipid biosynthetic process / Signal attenuation / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / negative regulation of gluconeogenesis / positive regulation of nitric oxide mediated signal transduction / regulation of protein localization to plasma membrane / COPI-mediated anterograde transport / phosphatidylinositol 3-kinase binding / negative regulation of lipid catabolic process / heart morphogenesis / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / positive regulation of insulin receptor signaling pathway / 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 / receptor-mediated endocytosis / NPAS4 regulates expression of target genes / positive regulation of protein metabolic process / neuron projection maintenance / endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of brown fat cell differentiation / activation of protein kinase B activity / positive regulation of glycolytic process / Insulin receptor signalling cascade / positive regulation of mitotic nuclear division / learning / Regulation of insulin secretion / positive regulation of nitric-oxide synthase activity / positive regulation of long-term synaptic potentiation / caveola / endosome lumen / positive regulation of cytokine production / acute-phase response / positive regulation of protein secretion / regulation of transmembrane transporter activity / positive regulation of cell differentiation / positive regulation of glucose import / negative regulation of proteolysis / regulation of synaptic plasticity / positive regulation of MAP kinase activity / wound healing / insulin receptor binding / negative regulation of protein catabolic process / positive regulation of neuron projection development / hormone activity / receptor internalization / receptor protein-tyrosine kinase / memory / cellular response to growth factor stimulus / cognition / Golgi lumen Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) / Ovis aries (sheep) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 7.4 Å | ||||||||||||
Authors | Scapin G / Dandey VP / Zhang Z / Strickland C / Potter CS / Carragher B | ||||||||||||
Funding support | United States, 3 items
| ||||||||||||
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 |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_7461.map.gz | 70.1 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-7461-v30.xml emd-7461.xml | 17.4 KB 17.4 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_7461_fsc.xml | 12 KB | Display | FSC data file |
Images | emd_7461.png | 53.7 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-7461 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-7461 | HTTPS FTP |
-Related structure data
Related structure data | 6ce7MC 7462C 7463C 6ce9C 6cebC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_7461.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Insulin receptor dimer with one insulin bound | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-Sample components
-Entire : Insulin Receptor Ectodomain in complex with one insulin molecule
Entire | Name: Insulin Receptor Ectodomain in complex with one insulin molecule |
---|---|
Components |
|
-Supramolecule #1: Insulin Receptor Ectodomain in complex with one insulin molecule
Supramolecule | Name: Insulin Receptor Ectodomain in complex with one insulin molecule type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
---|---|
Molecular weight | Theoretical: 215 KDa |
-Supramolecule #2: Insulin receptor
Supramolecule | Name: Insulin receptor / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Mus musculus (house mouse) |
-Supramolecule #3: Insulin A chain
Supramolecule | Name: Insulin A chain / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #4: Insulin B chain
Supramolecule | Name: Insulin B chain / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #3 |
---|---|
Source (natural) | Organism: Ovis aries (sheep) |
-Supramolecule #5: Insulin receptor subunit alpha
Supramolecule | Name: Insulin receptor subunit alpha / type: complex / ID: 5 / Parent: 1 / Macromolecule list: #4 |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Mus musculus (house mouse) |
-Macromolecule #1: Insulin receptor
Macromolecule | Name: Insulin receptor / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO / EC number: receptor protein-tyrosine kinase |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 105.926094 KDa |
Recombinant expression | Organism: Mus musculus (house mouse) |
Sequence | String: HLYPGEVCPG MDIRNNLTRL HELENCSVIE GHLQILLMFK TRPEDFRDLS FPKLIMITDY LLLFRVYGLE SLKDLFPNLT VIRGSRLFF NYALVIFEMV HLKELGLYNL MNITRGSVRI EKNNELCYLA TIDWSRILDS VEDNHIVLNK DDNEECGDIC P GTAKGKTN ...String: HLYPGEVCPG MDIRNNLTRL HELENCSVIE GHLQILLMFK TRPEDFRDLS FPKLIMITDY LLLFRVYGLE SLKDLFPNLT VIRGSRLFF NYALVIFEMV HLKELGLYNL MNITRGSVRI EKNNELCYLA TIDWSRILDS VEDNHIVLNK DDNEECGDIC P GTAKGKTN CPATVINGQF VERCWTHSHC QKVCPTICKS HGCTAEGLCC HSECLGNCSQ PDDPTKCVAC RNFYLDGRCV ET CPPPYYH FQDWRCVNFS FCQDLHHKCK NSRRQGCHQY VIHNNKCIPE CPSGYTMNSS NLLCTPCLGP CPKVCHLLEG EKT IDSVTS AQELRGCTVI NGSLIINIRG GNNLAAELEA NLGLIEEISG YLKIRRSYAL VSLSFFRKLR LIRGETLEIG NYSF YALDN QNLRQLWDWS KHNLTITQGK LFFHYNPKLC LSEIHKMEEV SGTKGRQERN DIALKTNGDQ ASCENELLKF SYIRT SFDK ILLRWEPYWP PDFRDLLGFM LFYKEAPYQN VTEFDGQDAC GSNSWTVVDI DPPLRSNDPK SQNHPGWLMR GLKPWT QYA IFVKTLVTFS DERRTYGAKS DIIYVQTDAT NPSVPLDPIS VSNSSSQIIL KWKPPSDPNG NITHYLVFWE RQAEDSE LF ELDYCLKGLK LPSRTWSPPF ESEDSQKHNQ SEYEDSAGEC CSCPKTDSQI LKELEESSFR KTFEDYLHNV VFVPRKTS S GTGAEDPRPS RKRRSLGDVG NVTVAVPTVA AFPNTSSTSV PTSPEEHRPF EKVVNKESLV ISGLRHFTGY RIELQACNQ DTPEERCSVA AYVSARTMPE AKADDIVGPV THEIFENNVV HLMWQEPKEP NGLIVLYEVS YRRYGDEELH LCVSRKHFAL ERGCRLRGL SPGNYSVRIR ATSLAGNGSW TEPTYFYVTD YLDVPSNIAK |
-Macromolecule #2: Insulin A chain
Macromolecule | Name: Insulin A chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 2.383698 KDa |
Sequence | String: GIVEQCCTSI CSLYQLENYC N |
-Macromolecule #3: Insulin B chain
Macromolecule | Name: Insulin B chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Ovis aries (sheep) |
Molecular weight | Theoretical: 3.403927 KDa |
Sequence | String: FVNQHLCGSH LVEALYLVCG ERGFFYTPKA |
-Macromolecule #4: Insulin receptor subunit alpha
Macromolecule | Name: Insulin receptor subunit alpha / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO / EC number: receptor protein-tyrosine kinase |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 3.671163 KDa |
Recombinant expression | Organism: Mus musculus (house mouse) |
Sequence | String: QILKELEESS FRKTFEDYLH NVVFVPRPSR |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.3 mg/mL |
---|---|
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 |
---|---|
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Detector mode: COUNTING / Average electron dose: 45.5 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
-Atomic model buiding 1
Refinement | Protocol: RIGID BODY FIT |
---|---|
Output model | PDB-6ce7: |