[English] 日本語
Yorodumi
- EMDB-28693: Cryo-EM structure of two IGF1 bound full-length mouse IGF1R mutan... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-28693
TitleCryo-EM structure of two IGF1 bound full-length mouse IGF1R mutant (four glycine residues inserted in the alpha-CT; IGF1R-P674G4): symmetric conformation
Map dataCryo-EM structure of two IGF1 bound full-length mouse IGF1R mutant (four glycine residues inserted in the alpha-CT; IGF1R-P674G4): symmetric conformation
Sample
  • Complex: Two IGF1 bound full-length mouse IGF1R mutant (four glycine residues inserted in the alpha-CT; IGF1R-P674G4): symmetric conformation
    • Protein or peptide: Insulin-like growth factor 1 receptor
    • Protein or peptide: Insulin-like growth factor I
KeywordsIGF1R / IGF1 / SIGNALING PROTEIN
Function / homology
Function and homology information


Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / IRS-related events triggered by IGF1R / SHC-related events triggered by IGF1R / mitotic nuclear division / glycolate metabolic process / muscle hypertrophy / negative regulation of oocyte development / positive regulation of trophectodermal cell proliferation / insulin-like growth factor binding protein complex / insulin-like growth factor ternary complex ...Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / IRS-related events triggered by IGF1R / SHC-related events triggered by IGF1R / mitotic nuclear division / glycolate metabolic process / muscle hypertrophy / negative regulation of oocyte development / positive regulation of trophectodermal cell proliferation / insulin-like growth factor binding protein complex / insulin-like growth factor ternary complex / positive regulation of glycoprotein biosynthetic process / proteoglycan biosynthetic process / myotube cell development / Extra-nuclear estrogen signaling / negative regulation of neuroinflammatory response / positive regulation of transcription regulatory region DNA binding / insulin-like growth factor binding / Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration / bone mineralization involved in bone maturation / positive regulation of cell growth involved in cardiac muscle cell development / IRS-related events triggered by IGF1R / negative regulation of vascular associated smooth muscle cell apoptotic process / exocytic vesicle / positive regulation of meiotic cell cycle / cell activation / positive regulation of developmental growth / positive regulation of calcineurin-NFAT signaling cascade / prostate gland epithelium morphogenesis / male sex determination / transmembrane receptor protein tyrosine kinase activator activity / mammary gland development / exocrine pancreas development / alphav-beta3 integrin-IGF-1-IGF1R complex / cell surface receptor signaling pathway via STAT / myoblast differentiation / positive regulation of Ras protein signal transduction / positive regulation of insulin-like growth factor receptor signaling pathway / myoblast proliferation / growth hormone receptor signaling pathway / negative regulation of interleukin-1 beta production / positive regulation of DNA binding / adrenal gland development / muscle organ development / positive regulation of smooth muscle cell migration / positive regulation of cardiac muscle hypertrophy / negative regulation of release of cytochrome c from mitochondria / negative regulation of amyloid-beta formation / negative regulation of smooth muscle cell apoptotic process / positive regulation of activated T cell proliferation / insulin receptor substrate binding / negative regulation of tumor necrosis factor production / Synthesis, secretion, and deacylation of Ghrelin / epidermis development / epithelial to mesenchymal transition / negative regulation of MAPK cascade / positive regulation of glycogen biosynthetic process / SHC-related events triggered by IGF1R / phosphatidylinositol 3-kinase binding / postsynaptic modulation of chemical synaptic transmission / positive regulation of osteoblast differentiation / activation of protein kinase B activity / positive regulation of vascular associated smooth muscle cell proliferation / insulin-like growth factor receptor binding / T-tubule / positive regulation of mitotic nuclear division / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / insulin-like growth factor receptor signaling pathway / platelet alpha granule lumen / positive regulation of glycolytic process / positive regulation of epithelial cell proliferation / animal organ morphogenesis / skeletal system development / negative regulation of extrinsic apoptotic signaling pathway / positive regulation of D-glucose import / positive regulation of protein secretion / phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of smooth muscle cell proliferation / insulin receptor binding / growth factor activity / wound healing / 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 / brain development / receptor protein-tyrosine kinase
Similarity search - Function
Insulin-like growth factor I / Insulin-like growth factor / Tyrosine-protein kinase, insulin-like receptor / Tyrosine-protein kinase, receptor class II, conserved site / Receptor tyrosine kinase class II signature. / Insulin family / Insulin-like / Insulin/IGF/Relaxin family / Insulin / insulin-like growth factor / relaxin family. / Insulin, conserved site ...Insulin-like growth factor I / Insulin-like growth factor / Tyrosine-protein kinase, insulin-like receptor / Tyrosine-protein kinase, receptor class II, conserved site / Receptor tyrosine kinase class II signature. / Insulin family / Insulin-like / Insulin/IGF/Relaxin family / Insulin / insulin-like growth factor / relaxin family. / Insulin, conserved site / Insulin family signature. / Insulin-like superfamily / 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 / Insulin-like growth factor 1 receptor
Similarity search - Component
Biological speciesMus musculus (house mouse) / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 4.0 Å
AuthorsLi J / Wu JY / Hall C / Bai XC / Choi E
Funding support United States, 2 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R01GM136976 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R35GM142937 United States
CitationJournal: Elife / Year: 2022
Title: Molecular basis for the role of disulfide-linked αCTs in the activation of insulin-like growth factor 1 receptor and insulin receptor.
Authors: Jie Li / Jiayi Wu / Catherine Hall / Xiao-Chen Bai / Eunhee Choi /
Abstract: The insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) control metabolic homeostasis and cell growth and proliferation. The IR and IGF1R form similar disulfide bonds linked ...The insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) control metabolic homeostasis and cell growth and proliferation. The IR and IGF1R form similar disulfide bonds linked homodimers in the apo-state; however, their ligand binding properties and the structures in the active state differ substantially. It has been proposed that the disulfide-linked C-terminal segment of α-chain (αCTs) of the IR and IGF1R control the cooperativity of ligand binding and regulate the receptor activation. Nevertheless, the molecular basis for the roles of disulfide-linked αCTs in IR and IGF1R activation are still unclear. Here, we report the cryo-EM structures of full-length mouse IGF1R/IGF1 and IR/insulin complexes with modified αCTs that have increased flexibility. Unlike the -shaped asymmetric IGF1R dimer with a single IGF1 bound, the IGF1R with the enhanced flexibility of αCTs can form a -shaped symmetric dimer with two IGF1s bound. Meanwhile, the IR with non-covalently linked αCTs predominantly adopts an asymmetric conformation with four insulins bound, which is distinct from the -shaped symmetric IR. Using cell-based experiments, we further showed that both IGF1R and IR with the modified αCTs cannot activate the downstream signaling potently. Collectively, our studies demonstrate that the certain structural rigidity of disulfide-linked αCTs is critical for optimal IR and IGF1R signaling activation.
History
DepositionOct 28, 2022-
Header (metadata) releaseNov 9, 2022-
Map releaseNov 9, 2022-
UpdateOct 23, 2024-
Current statusOct 23, 2024Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_28693.png

Downloads & links

-
Map

FileDownload / File: emd_28693.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationCryo-EM structure of two IGF1 bound full-length mouse IGF1R mutant (four glycine residues inserted in the alpha-CT; IGF1R-P674G4): symmetric conformation
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 360 pix.
= 298.8 Å		0.83 Å/pix.
x 360 pix.
= 298.8 Å		0.83 Å/pix.
x 360 pix.
= 298.8 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.83 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.006
Minimum - Maximum-0.026597057 - 0.049789708
Average (Standard dev.)0.000050296665 (±0.0010395781)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions360360360
Spacing360360360
CellA=B=C: 298.8 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: Cryo-EM structure of two IGF1 bound full-length mouse...

Fileemd_28693_half_map_1.map
AnnotationCryo-EM structure of two IGF1 bound full-length mouse IGF1R mutant (four glycine residues inserted in the alpha-CT; IGF1R-P674G4): symmetric conformation Unfiltered half1 map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: Cryo-EM structure of two IGF1 bound full-length mouse...

Fileemd_28693_half_map_2.map
AnnotationCryo-EM structure of two IGF1 bound full-length mouse IGF1R mutant (four glycine residues inserted in the alpha-CT; IGF1R-P674G4): symmetric conformation Unfiltered half2 map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Two IGF1 bound full-length mouse IGF1R mutant (four glycine resid...

EntireName: Two IGF1 bound full-length mouse IGF1R mutant (four glycine residues inserted in the alpha-CT; IGF1R-P674G4): symmetric conformation
Components
  • Complex: Two IGF1 bound full-length mouse IGF1R mutant (four glycine residues inserted in the alpha-CT; IGF1R-P674G4): symmetric conformation
    • Protein or peptide: Insulin-like growth factor 1 receptor
    • Protein or peptide: Insulin-like growth factor I

-
Supramolecule #1: Two IGF1 bound full-length mouse IGF1R mutant (four glycine resid...

SupramoleculeName: Two IGF1 bound full-length mouse IGF1R mutant (four glycine residues inserted in the alpha-CT; IGF1R-P674G4): symmetric conformation
type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Mus musculus (house mouse)

-
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: Mus musculus (house mouse)
Molecular weightTheoretical: 144.481953 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: EICGPGIDIR NDYQQLKRLE NCTVIEGFLH ILLISKAEDY RSYRFPKLTV ITEYLLLFRV AGLESLGDLF PNLTVIRGWK LFYNYALVI FEMTNLKDIG LYNLRNITRG AIRIEKNADL CYLSTIDWSL ILDAVSNNYI VGNKPPKECG DLCPGTLEEK P MCEKTTIN ...String:
EICGPGIDIR NDYQQLKRLE NCTVIEGFLH ILLISKAEDY RSYRFPKLTV ITEYLLLFRV AGLESLGDLF PNLTVIRGWK LFYNYALVI FEMTNLKDIG LYNLRNITRG AIRIEKNADL CYLSTIDWSL ILDAVSNNYI VGNKPPKECG DLCPGTLEEK P MCEKTTIN NEYNYRCWTT NRCQKMCPSV CGKRACTENN ECCHPECLGS CHTPDDNTTC VACRHYYYKG VCVPACPPGT YR FEGWRCV DRDFCANIPN AESSDSDGFV IHDDECMQEC PSGFIRNSTQ SMYCIPCEGP CPKVCGDEEK KTKTIDSVTS AQM LQGCTI LKGNLLINIR RGNNIASELE NFMGLIEVVT GYVKIRHSHA LVSLSFLKNL RLILGEEQLE GNYSFYVLDN QNLQ QLWDW NHRNLTVRSG KMYFAFNPKL CVSEIYRMEE VTGTKGRQSK GDINTRNNGE RASCESDVLR FTSTTTWKNR IIITW HRYR PPDYRDLISF TVYYKEAPFK NVTEYDGQDA CGSNSWNMVD VDLPPNKEGE PGILLHGLKP WTQYAVYVKA VTLTMV END HIRGAKSEIL YIRTNASVPS IPLDVLSASN SSSQLIVKWN PPTLPNGNLS YYIVRWQRQP QDGYLYRHNY CSKDKIP IR KYADGTIDVE EVTENPKTEV CGGDKGPCCA CPGGGGKTEA EKQAEKEEAE YRKVFENFLH NSIFVPRPER RRRDVMQV A NTTMSSRSRN TTVADTYNIT DPEEFETEYP FFESRVDNKE RTVISNLRPF TLYRIDIHSC NHEAEKLGCS ASNFVFART MPAEGADDIP GPVTWEPRPE NSIFLKWPEP ENPNGLILMY EIKYGSQVED QRECVSRQEY RKYGGAKLNR LNPGNYTARI QATSLSGNG SWTDPVFFYV PAKTTYENFM HLIIALPVAI LLIVGGLVIM LYVFHRKRNN SRLGNGVLYA SVNPEYFSAA D VYVPDEWE VAREKITMNR ELGQGSFGMV YEGVAKGVVK DEPETRVAIK TVNEAASMRE RIEFLNEASV MKEFNCHHVV RL LGVVSQG QPTLVIMELM TRGDLKSYLR SLRPEVEQNN LVLIPPSLSK MIQMAGEIAD GMAYLNANKF VHRDLAARNC MVA EDFTVK IGDFGMTRDI YETDYYRKGG KGLLPVRWMS PESLKDGVFT THSDVWSFGV VLWEIATLAE QPYQGLSNEQ VLRF VMEGG LLDKPDNCPD MLFELMRMCW QYNPKMRPSF LEIIGSIKDE MEPSFQEVSF YYSEENKPPE P

UniProtKB: Insulin-like growth factor 1 receptor

-
Macromolecule #2: Insulin-like growth factor I

MacromoleculeName: Insulin-like growth factor I / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 21.88132 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: MGKISSLPTQ LFKCCFCDFL KVKMHTMSSS HLFYLALCLL TFTSSATAGP ETLCGAELVD ALQFVCGDRG FYFNKPTGYG SSSRRAPQT GIVDECCFRS CDLRRLEMYC APLKPAKSAR SVRAQRHTDM PKTQKYQPPS TNKNTKSQRR KGWPKTHPGG E QKEGTEAS ...String:
MGKISSLPTQ LFKCCFCDFL KVKMHTMSSS HLFYLALCLL TFTSSATAGP ETLCGAELVD ALQFVCGDRG FYFNKPTGYG SSSRRAPQT GIVDECCFRS CDLRRLEMYC APLKPAKSAR SVRAQRHTDM PKTQKYQPPS TNKNTKSQRR KGWPKTHPGG E QKEGTEAS LQIRGKKKEQ RREIGSRNAE CRGKKGK

UniProtKB: Insulin-like growth factor 1

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration6 mg/mL
BufferpH: 7.4
GridModel: Quantifoil / Material: GOLD / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Specialist opticsEnergy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.6 µm / Nominal defocus min: 1.6 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Particle selectionNumber selected: 1909017
Startup modelType of model: OTHER
Final reconstructionApplied symmetry - Point group: C2 (2 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 4.0 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION / Number images used: 21684
Initial angle assignmentType: PROJECTION MATCHING / Software - Name: RELION
Final angle assignmentType: PROJECTION MATCHING / Software - Name: RELION
Final 3D classificationSoftware - Name: RELION

+
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