[English] 日本語
Yorodumi
- EMDB-26306: Single-chain LCDV-1 viral insulin-like peptide bound to IGF-1R ec... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-26306
TitleSingle-chain LCDV-1 viral insulin-like peptide bound to IGF-1R ectodomain, leucine-zippered form
Map datacryoEM structure of scLCDV-1 VILP bound to IGF-1Rzip.
Sample
  • Complex: 2:1 complex of scLCDV-1 and IGF-1Rzip
    • Protein or peptide: Insulin-like growth factor 1 receptor
    • Protein or peptide: single-chain LCDV-1 viral insulin-like peptide
KeywordsIGF-1R ectodomain / inhibitor / viral insulin-like peptide / single-chain LCDV-1 / SIGNALING PROTEIN
Function / homology
Function and homology information


cardiac atrium development / negative regulation of cholangiocyte apoptotic process / positive regulation of steroid hormone biosynthetic process / protein kinase complex / insulin-like growth factor binding / Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / protein transporter activity / IRS-related events triggered by IGF1R / negative regulation of muscle cell apoptotic process / cellular response to progesterone stimulus ...cardiac atrium development / negative regulation of cholangiocyte apoptotic process / positive regulation of steroid hormone biosynthetic process / protein kinase complex / insulin-like growth factor binding / Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / protein transporter activity / IRS-related events triggered by IGF1R / 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 / cellular response to testosterone stimulus / insulin receptor complex / transcytosis / insulin-like growth factor I binding / negative regulation of hepatocyte apoptotic process / positive regulation of protein-containing complex disassembly / alphav-beta3 integrin-IGF-1-IGF1R complex / response to alkaloid / regulation of JNK cascade / dendritic spine maintenance / insulin binding / cellular response to insulin-like growth factor stimulus / response to L-glutamate / establishment of cell polarity / positive regulation of axon regeneration / positive regulation of osteoblast proliferation / positive regulation of cytokinesis / amyloid-beta clearance / Respiratory syncytial virus (RSV) attachment and entry / insulin receptor substrate binding / cellular response to angiotensin / response to vitamin E / G-protein alpha-subunit binding / negative regulation of MAPK cascade / SHC-related events triggered by IGF1R / phosphatidylinositol 3-kinase binding / peptidyl-tyrosine autophosphorylation / estrous cycle / cellular response to transforming growth factor beta stimulus / T-tubule / cerebellum development / cellular response to dexamethasone stimulus / axonogenesis / insulin-like growth factor receptor signaling pathway / hippocampus development / phosphatidylinositol 3-kinase/protein kinase B signal transduction / response to nicotine / positive regulation of smooth muscle cell proliferation / insulin receptor binding / cellular response to estradiol stimulus / placental growth factor receptor activity / cellular response to glucose stimulus / insulin receptor activity / vascular endothelial growth factor receptor activity / hepatocyte growth factor receptor activity / macrophage colony-stimulating factor receptor activity / platelet-derived growth factor alpha-receptor activity / platelet-derived growth factor beta-receptor activity / stem cell factor receptor activity / boss receptor activity / protein tyrosine kinase collagen receptor activity / brain-derived neurotrophic factor receptor activity / transmembrane-ephrin receptor activity / GPI-linked ephrin receptor activity / epidermal growth factor receptor activity / fibroblast growth factor receptor activity / insulin-like growth factor receptor activity / receptor protein-tyrosine kinase / caveola / cellular response to mechanical stimulus / cellular response to amyloid-beta / cellular senescence / insulin receptor signaling pathway / positive regulation of cold-induced thermogenesis / protein autophosphorylation / protein tyrosine kinase activity / response to ethanol / Extra-nuclear estrogen signaling / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor complex / positive regulation of MAPK cascade / immune response / cilium / positive regulation of cell migration / axon / neuronal cell body / intracellular membrane-bounded organelle / positive regulation of cell population proliferation / protein-containing complex binding / negative regulation of apoptotic process / nucleolus / signal transduction / ATP binding / identical protein binding / membrane / plasma membrane
Similarity search - Function
Tyrosine-protein kinase, insulin-like receptor / Tyrosine-protein kinase, receptor class II, conserved site / Receptor tyrosine kinase class II signature. / Receptor L-domain / Furin-like cysteine-rich domain / Receptor L-domain superfamily / Furin-like cysteine rich region / Receptor L domain / Furin-like repeat / Furin-like repeats ...Tyrosine-protein kinase, insulin-like receptor / Tyrosine-protein kinase, receptor class II, conserved site / Receptor tyrosine kinase class II signature. / Receptor L-domain / Furin-like cysteine-rich domain / Receptor L-domain superfamily / Furin-like cysteine rich region / Receptor L domain / Furin-like repeat / Furin-like repeats / Growth factor receptor cysteine-rich domain superfamily / : / Fibronectin type 3 domain / Fibronectin type-III domain profile. / Fibronectin type III / Fibronectin type III superfamily / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Immunoglobulin-like fold / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
Insulin-like growth factor 1 receptor
Similarity search - Component
Biological speciesHomo sapiens (human) / Lymphocystis disease virus 1
Methodsingle particle reconstruction / cryo EM / Resolution: 4.6 Å
AuthorsKirk NS / Lawrence MC
Funding support United States, 2 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)R01DK031036 United States
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)K01DK11796 United States
CitationJournal: 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
DepositionFeb 22, 2022-
Header (metadata) releaseNov 16, 2022-
Map releaseNov 16, 2022-
UpdateJun 4, 2025-
Current statusJun 4, 2025Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_26306.png

Downloads & links

-
Map

FileDownload / File: emd_26306.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationcryoEM structure of scLCDV-1 VILP bound to IGF-1Rzip.
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.06 Å/pix.
x 360 pix.
= 381.6 Å		1.06 Å/pix.
x 360 pix.
= 381.6 Å		1.06 Å/pix.
x 360 pix.
= 381.6 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.06 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy EMDB: 0.09
Minimum - Maximum-0.4494273 - 0.71132874
Average (Standard dev.)-0.0004327955 (±0.013158419)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions360360360
Spacing360360360
CellA=B=C: 381.59998 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: Half map A

Fileemd_26306_half_map_1.map
AnnotationHalf map A
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: Half map B

Fileemd_26306_half_map_2.map
AnnotationHalf map B
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : 2:1 complex of scLCDV-1 and IGF-1Rzip

EntireName: 2:1 complex of scLCDV-1 and IGF-1Rzip
Components
  • Complex: 2:1 complex of scLCDV-1 and IGF-1Rzip
    • Protein or peptide: Insulin-like growth factor 1 receptor
    • Protein or peptide: single-chain LCDV-1 viral insulin-like peptide

-
Supramolecule #1: 2:1 complex of scLCDV-1 and IGF-1Rzip

SupramoleculeName: 2:1 complex of scLCDV-1 and IGF-1Rzip / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Insulin-like growth factor 1 receptor

MacromoleculeName: Insulin-like growth factor 1 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 weightTheoretical: 108.937242 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString: 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

UniProtKB: Insulin-like growth factor 1 receptor

-
Macromolecule #2: single-chain LCDV-1 viral insulin-like peptide

MacromoleculeName: single-chain LCDV-1 viral insulin-like peptide / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Lymphocystis disease virus 1
Molecular weightTheoretical: 6.72671 KDa
SequenceString:
ITAEILCSAH LVAALQRVCG NRGVYRPPPT RRRSTRNGTT GIATKCCTTT GCTTDDLEKY CN

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration0.1 mg/mL
BufferpH: 8
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.5 µm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 4.6 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 89000
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

-
Atomic model buiding 1

RefinementSpace: REAL
Output model

PDB-7u23:
Single-chain LCDV-1 viral insulin-like peptide bound to IGF-1R ectodomain, leucine-zippered form

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more