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Yorodumi- EMDB-26306: Single-chain LCDV-1 viral insulin-like peptide bound to IGF-1R ec... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-26306 | |||||||||
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Title | Single-chain LCDV-1 viral insulin-like peptide bound to IGF-1R ectodomain, leucine-zippered form | |||||||||
Map data | cryoEM structure of scLCDV-1 VILP bound to IGF-1Rzip. | |||||||||
Sample |
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Function / homology | Function and homology information cardiac atrium development / negative regulation of cholangiocyte apoptotic process / 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) / IRS-related events triggered by IGF1R / insulin-like growth factor binding / protein transporter activity / negative regulation of muscle cell apoptotic process ...cardiac atrium development / negative regulation of cholangiocyte apoptotic process / 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) / IRS-related events triggered by IGF1R / insulin-like growth factor binding / protein transporter activity / negative regulation of muscle cell apoptotic process / cellular response to progesterone stimulus / positive regulation of DNA metabolic process / cellular response to zinc ion starvation / cellular response to aldosterone / insulin receptor complex / cellular response to testosterone stimulus / negative regulation of hepatocyte apoptotic process / insulin-like growth factor I binding / insulin receptor activity / transcytosis / alphav-beta3 integrin-IGF-1-IGF1R complex / response to alkaloid / Respiratory syncytial virus (RSV) attachment and entry / regulation of JNK cascade / cellular response to angiotensin / positive regulation of protein-containing complex disassembly / dendritic spine maintenance / cellular response to insulin-like growth factor stimulus / insulin binding / response to L-glutamate / negative regulation of MAPK cascade / establishment of cell polarity / positive regulation of axon regeneration / amyloid-beta clearance / positive regulation of osteoblast proliferation / positive regulation of cytokinesis / peptidyl-tyrosine autophosphorylation / insulin receptor substrate binding / estrous cycle / G-protein alpha-subunit binding / response to vitamin E / SHC-related events triggered by IGF1R / cellular response to dexamethasone stimulus / phosphatidylinositol 3-kinase binding / cellular response to transforming growth factor beta stimulus / T-tubule / cellular response to estradiol stimulus / phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of smooth muscle cell proliferation / cerebellum development / axonogenesis / insulin-like growth factor receptor signaling pathway / caveola / hippocampus development / receptor protein-tyrosine kinase / cellular response to glucose stimulus / insulin receptor binding / response to nicotine / cellular response to mechanical stimulus / cellular senescence / cellular response to amyloid-beta / insulin receptor signaling pathway / positive regulation of cold-induced thermogenesis / protein tyrosine kinase activity / response to ethanol / protein autophosphorylation / Extra-nuclear estrogen signaling / receptor complex / positive regulation of MAPK cascade / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of cell migration / immune response / axon / intracellular membrane-bounded organelle / neuronal cell body / positive regulation of cell population proliferation / negative regulation of apoptotic process / protein-containing complex binding / signal transduction / ATP binding / identical protein binding / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Lymphocystis disease virus 1 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.6 Å | |||||||||
Authors | Kirk NS / Lawrence MC | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Nat Commun / Year: 2022 Title: Interaction of a viral insulin-like peptide with the IGF-1 receptor produces a natural antagonist. Authors: Francois Moreau / Nicholas S Kirk / Fa Zhang / Vasily Gelfanov / Edward O List / Martina Chrudinová / Hari Venugopal / Michael C Lawrence / Veronica Jimenez / Fatima Bosch / John J Kopchick ...Authors: Francois Moreau / Nicholas S Kirk / Fa Zhang / Vasily Gelfanov / Edward O List / Martina Chrudinová / Hari Venugopal / Michael C Lawrence / Veronica Jimenez / Fatima Bosch / John J Kopchick / Richard D DiMarchi / Emrah Altindis / C Ronald Kahn / Abstract: Lymphocystis disease virus-1 (LCDV-1) and several other Iridoviridae encode viral insulin/IGF-1 like peptides (VILPs) with high homology to human insulin and IGFs. Here we show that while single- ...Lymphocystis disease virus-1 (LCDV-1) and several other Iridoviridae encode viral insulin/IGF-1 like peptides (VILPs) with high homology to human insulin and IGFs. Here we show that while single-chain (sc) and double-chain (dc) LCDV1-VILPs have very low affinity for the insulin receptor, scLCDV1-VILP has high affinity for IGF1R where it can antagonize human IGF-1 signaling, without altering insulin signaling. Consequently, scLCDV1-VILP inhibits IGF-1 induced cell proliferation and growth hormone/IGF-1 induced growth of mice in vivo. Cryo-electron microscopy reveals that scLCDV1-VILP engages IGF1R in a unique manner, inducing changes in IGF1R conformation that led to separation, rather than juxtaposition, of the transmembrane segments and hence inactivation of the receptor. Thus, scLCDV1-VILP is a natural peptide with specific antagonist properties on IGF1R signaling and may provide a new tool to guide development of hormonal analogues to treat cancers or metabolic disorders sensitive to IGF-1 without affecting glucose metabolism. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_26306.map.gz | 167.9 MB | EMDB map data format | |
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Header (meta data) | emd-26306-v30.xml emd-26306.xml | 17.1 KB 17.1 KB | Display Display | EMDB header |
Images | emd_26306.png | 58.6 KB | ||
Others | emd_26306_half_map_1.map.gz emd_26306_half_map_2.map.gz | 165.2 MB 165.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-26306 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26306 | HTTPS FTP |
-Validation report
Summary document | emd_26306_validation.pdf.gz | 779.5 KB | Display | EMDB validaton report |
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Full document | emd_26306_full_validation.pdf.gz | 779 KB | Display | |
Data in XML | emd_26306_validation.xml.gz | 14.8 KB | Display | |
Data in CIF | emd_26306_validation.cif.gz | 17.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26306 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26306 | HTTPS FTP |
-Related structure data
Related structure data | 7u23MC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_26306.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | cryoEM structure of scLCDV-1 VILP bound to IGF-1Rzip. | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.06 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: Half map A
File | emd_26306_half_map_1.map | ||||||||||||
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Annotation | Half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map B
File | emd_26306_half_map_2.map | ||||||||||||
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Annotation | Half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : 2:1 complex of scLCDV-1 and IGF-1Rzip
Entire | Name: 2:1 complex of scLCDV-1 and IGF-1Rzip |
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Components |
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-Supramolecule #1: 2:1 complex of scLCDV-1 and IGF-1Rzip
Supramolecule | Name: 2:1 complex of scLCDV-1 and IGF-1Rzip / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Insulin-like growth factor 1 receptor
Macromolecule | Name: Insulin-like growth factor 1 receptor / 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: Homo sapiens (human) |
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: single-chain LCDV-1 viral insulin-like peptide
Macromolecule | Name: single-chain LCDV-1 viral insulin-like peptide / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Lymphocystis disease virus 1 |
Molecular weight | Theoretical: 6.72671 KDa |
Sequence | String: ITAEILCSAH LVAALQRVCG NRGVYRPPPT RRRSTRNGTT GIATKCCTTT GCTTDDLEKY CN |
-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: 8 |
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV |
-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 / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.5 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 4.6 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 89000 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
-Atomic model buiding 1
Refinement | Space: REAL |
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Output model | PDB-7u23: |