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Yorodumi- EMDB-21415: Head region of the open conformation of the human type 1 insulin-... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-21415 | |||||||||
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Title | Head region of the open conformation of the human type 1 insulin-like growth factor receptor ectodomain in complex with human insulin-like growth factor II. | |||||||||
Map data | Focused refinement | |||||||||
Sample |
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Function / homology | Function and homology information spongiotrophoblast cell proliferation / cardiac atrium development / positive regulation of skeletal muscle tissue growth / negative regulation of cholangiocyte apoptotic process / negative regulation of muscle cell differentiation / embryonic placenta morphogenesis / regulation of muscle cell differentiation / insulin-like growth factor receptor activity / positive regulation of steroid hormone biosynthetic process / protein kinase complex ...spongiotrophoblast cell proliferation / cardiac atrium development / positive regulation of skeletal muscle tissue growth / negative regulation of cholangiocyte apoptotic process / negative regulation of muscle cell differentiation / embryonic placenta morphogenesis / regulation of muscle cell differentiation / insulin-like growth factor receptor activity / positive regulation of steroid hormone biosynthetic process / protein kinase complex / Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / protein transporter activity / IRS-related events triggered by IGF1R / insulin-like growth factor binding / genomic imprinting / negative regulation of muscle cell apoptotic process / cellular response to progesterone stimulus / positive regulation of DNA metabolic process / positive regulation of organ growth / protein localization to nuclear periphery / FCERI mediated MAPK activation / cellular response to zinc ion starvation / cellular response to aldosterone / Activation of the AP-1 family of transcription factors / response to amino acid starvation / mediator complex binding / negative regulation of ribosomal protein gene transcription by RNA polymerase II / positive regulation of cellular response to amino acid starvation / exocrine pancreas development / insulin receptor complex / cellular response to testosterone stimulus / negative regulation of hepatocyte apoptotic process / insulin-like growth factor I binding / positive regulation of multicellular organism growth / insulin receptor activity / transcytosis / Oxidative Stress Induced Senescence / nitrogen catabolite activation of transcription from RNA polymerase II promoter / alphav-beta3 integrin-IGF-1-IGF1R complex / response to alkaloid / positive regulation of protein-containing complex disassembly / cellular response to angiotensin / dendritic spine maintenance / positive regulation of vascular endothelial cell proliferation / cellular response to insulin-like growth factor stimulus / response to L-glutamate / insulin binding / negative regulation of MAPK cascade / establishment of cell polarity / transmembrane receptor protein tyrosine kinase activator activity / positive regulation of activated T cell proliferation / positive regulation of axon regeneration / amyloid-beta clearance / positive regulation of osteoblast proliferation / positive regulation of cytokinesis / TFIID-class transcription factor complex binding / regulation of JNK cascade / positive regulation of cell division / insulin receptor substrate binding / estrous cycle / positive regulation of glycogen biosynthetic process / G-protein alpha-subunit binding / positive regulation of transcription initiation by RNA polymerase II / response to vitamin E / embryonic placenta development / amino acid biosynthetic process / SHC-related events triggered by IGF1R / positive regulation of RNA polymerase II transcription preinitiation complex assembly / phosphatidylinositol 3-kinase binding / positive regulation of insulin receptor signaling pathway / peptidyl-tyrosine autophosphorylation / T-tubule / cellular response to transforming growth factor beta stimulus / striated muscle cell differentiation / insulin-like growth factor receptor binding / cellular response to amino acid starvation / protein serine/threonine kinase activator activity / axonogenesis / positive regulation of mitotic nuclear division / cerebellum development / cellular response to dexamethasone stimulus / insulin-like growth factor receptor signaling pathway / phosphatidylinositol 3-kinase/protein kinase B signal transduction / platelet alpha granule lumen / caveola / cellular response to estradiol stimulus / hippocampus development / cellular response to glucose stimulus / animal organ morphogenesis / positive regulation of smooth muscle cell proliferation / response to nicotine / growth factor activity / insulin receptor binding / hormone activity / receptor protein-tyrosine kinase / osteoblast differentiation / cellular response to mechanical stimulus / RNA polymerase II transcription regulator complex / cellular response to amyloid-beta / glucose metabolic process Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (yeast) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.21 Å | |||||||||
Authors | Xu Y / Kirk NS / Lawrence MC / Croll TI | |||||||||
Funding support | Australia, United Kingdom, 2 items
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Citation | Journal: Structure / Year: 2020 Title: How IGF-II Binds to the Human Type 1 Insulin-like Growth Factor Receptor. Authors: Yibin Xu / Nicholas S Kirk / Hariprasad Venugopal / Mai B Margetts / Tristan I Croll / Jarrod J Sandow / Andrew I Webb / Carlie A Delaine / Briony E Forbes / Michael C Lawrence / Abstract: Human type 1 insulin-like growth factor receptor (IGF-1R) signals chiefly in response to the binding of insulin-like growth factor I. Relatively little is known about the role of insulin-like growth ...Human type 1 insulin-like growth factor receptor (IGF-1R) signals chiefly in response to the binding of insulin-like growth factor I. Relatively little is known about the role of insulin-like growth factor II signaling via IGF-1R, despite the affinity of insulin-like growth factor II for IGF-1R being within an order of magnitude of that of insulin-like growth factor I. Here, we describe the cryoelectron microscopy structure of insulin-like growth factor II bound to a leucine-zipper-stabilized IGF-1R ectodomain, determined in two conformations to a maximum average resolution of 3.2 Å. The two conformations differ in the relative separation of their respective points of membrane entry, and comparison with the structure of insulin-like growth factor I bound to IGF-1R reveals long-suspected differences in the way in which the critical C domain of the respective growth factors interact with IGF-1R. | |||||||||
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_21415.map.gz | 230 MB | EMDB map data format | |
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Header (meta data) | emd-21415-v30.xml emd-21415.xml | 18.7 KB 18.7 KB | Display Display | EMDB header |
Images | emd_21415.png | 22.3 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-21415 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-21415 | HTTPS FTP |
-Related structure data
Related structure data | 6vwgMC 6vwhC 6vwiC 6vwjC 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_21415.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Focused refinement | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
-Sample components
-Entire : Head region of the open-leg conformation of the human type 1 insu...
Entire | Name: Head region of the open-leg conformation of the human type 1 insulin-like growth factor receptor ectodomain in complex with human insulin-like growth factor II. |
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Components |
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-Supramolecule #1: Head region of the open-leg conformation of the human type 1 insu...
Supramolecule | Name: Head region of the open-leg conformation of the human type 1 insulin-like growth factor receptor ectodomain in complex with human insulin-like growth factor II. type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 250 KDa |
-Supramolecule #2: Insulin-like growth factor 1 receptor
Supramolecule | Name: Insulin-like growth factor 1 receptor / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Escherichia coli (E. coli) |
-Supramolecule #3: Insulin-like growth factor II
Supramolecule | Name: Insulin-like growth factor II / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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-Macromolecule #1: Leucine-zippered human type 1 insulin-like growth factor receptor...
Macromolecule | Name: Leucine-zippered human type 1 insulin-like growth factor receptor ectodomain type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO / EC number: receptor protein-tyrosine kinase |
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Source (natural) | Organism: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (yeast) Strain: ATCC 204508 / S288c |
Molecular weight | Theoretical: 108.937242 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: EICGPGIDIR NDYQQLKRLE NCTVIEGYLH ILLISKAEDY RSYRFPKLTV ITEYLLLFRV AGLESLGDLF PNLTVIRGWK LFYNYALVI FEMTNLKDIG LYNLRNITRG AIRIEKNADL CYLSTVDWSL ILDAVSNNYI VGNKPPKECG DLCPGTMEEK P MCEKTTIN ...String: EICGPGIDIR NDYQQLKRLE NCTVIEGYLH ILLISKAEDY RSYRFPKLTV ITEYLLLFRV AGLESLGDLF PNLTVIRGWK LFYNYALVI FEMTNLKDIG LYNLRNITRG AIRIEKNADL CYLSTVDWSL ILDAVSNNYI VGNKPPKECG DLCPGTMEEK P MCEKTTIN NEYNYRCWTT NRCQKMCPST CGKRACTENN ECCHPECLGS CSAPDNDTAC VACRHYYYAG VCVPACPPNT YR FEGWRCV DRDFCANILS AESSDSEGFV IHDGECMQEC PSGFIRNGSQ SMYCIPCEGP CPKVCEEEKK TKTIDSVTSA QML QGCTIF KGNLLINIRR GNNIASELEN FMGLIEVVTG YVKIRHSHAL VSLSFLKNLR LILGEEQLEG NYSFYVLDNQ NLQQ LWDWD HRNLTIKAGK MYFAFNPKLC VSEIYRMEEV TGTKGRQSKG DINTRNNGER ASCESDVLHF TSTTTSKNRI IITWH RYRP PDYRDLISFT VYYKEAPFKN VTEYDGQDAC GSNSWNMVDV DLPPNKDVEP GILLHGLKPW TQYAVYVKAV TLTMVE NDH IRGAKSEILY IRTNASVPSI PLDVLSASNS SSQLIVKWNP PSLPNGNLSY YIVRWQRQPQ DGYLYRHNYC SKDKIPI RK YADGTIDIEE VTENPKTEVC GGEKGPCCAC PKTEAEKQAE KEEAEYRKVF ENFLHNSIFV PRPERKRRDV MQVANTTM S SRSRNTTAAD TYNITDPEEL ETEYPFFESR VDNKERTVIS NLRPFTLYRI DIHSCNHEAE KLGCSASNFV FARTMPAEG ADDIPGPVTW EPRPENSIFL KWPEPENPNG LILMYEIKYG SQVEDQRECV SRQEYRKYGG AKLNRLNPGN YTARIQATSL SGNGSWTDP VFFYVQAKTG YENFIHRMKQ LEDKVEELLS KNYHLENEVA RLKKLVGERS SSEQKLISEE DLN |
-Macromolecule #2: Insulin-like growth factor II
Macromolecule | Name: Insulin-like growth factor II / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 7.484472 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: AYRPSETLCG GELVDTLQFV CGDRGFYFSR PASRVSRRSR GIVEECCFRS CDLALLETYC ATPAKSE |
-Macromolecule #3: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 3 / Number of copies: 4 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.1 mg/mL | ||||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil, UltrAuFoil, R1.2/1.3 / Material: GOLD / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE / Details: 15mA current | ||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV | ||||||||||
Details | IGFII:IGF-1R molar ratio 1.5:1 |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm |
Specialist optics | Energy filter - Name: GIF Quantum LS |
Sample stage | Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Digitization - Frames/image: 1-50 / Number grids imaged: 1 / Number real images: 4585 / Average exposure time: 10.0 sec. / Average electron dose: 50.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Particle selection | Number selected: 2057701 |
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CTF correction | Software - Name: CTFFIND (ver. 4.1.13) |
Startup model | Type of model: OTHER Details: Initial model was of the same ectodomain construct in complex with IGF-I (unpublished data). |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 2.11) |
Final 3D classification | Number classes: 7 / Software - Name: cryoSPARC (ver. 2.11) |
Final angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 2.11) |
Final reconstruction | Number classes used: 1 / Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.21 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 2.11) / Number images used: 205471 |
-Atomic model buiding 1
Initial model | PDB ID: |
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Details | UCSF Chimera was used for the initial fitting and ISOLDE v 1.03b was using for flexible fitting. |
Refinement | Space: REAL / Protocol: FLEXIBLE FIT |
Output model | PDB-6vwg: |