[English] 日本語
Yorodumi
- PDB-6pyh: Cryo-EM structure of full-length IGF1R-IGF1 complex. Only the ext... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6pyh
TitleCryo-EM structure of full-length IGF1R-IGF1 complex. Only the extracellular region of the complex is resolved.
Components
  • Insulin-like growth factor 1 receptor
  • Insulin-like growth factor I
KeywordsSIGNALING PROTEIN/HORMONE / IGF1R / IGF1 / SIGNALING PROTEIN-HORMONE complex
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 / insulin-like growth factor binding protein complex / insulin-like growth factor ternary complex / positive regulation of trophectodermal cell proliferation ...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 / insulin-like growth factor binding protein complex / insulin-like growth factor ternary complex / positive regulation of trophectodermal cell proliferation / prostate gland stromal morphogenesis / positive regulation of type B pancreatic cell proliferation / positive regulation of glycoprotein biosynthetic process / type II pneumocyte differentiation / neuronal dense core vesicle lumen / proteoglycan biosynthetic process / regulation of establishment or maintenance of cell polarity / chondroitin sulfate proteoglycan biosynthetic process / insulin-like growth factor receptor activity / myotube cell development / positive regulation of transcription regulatory region DNA binding / Extra-nuclear estrogen signaling / negative regulation of neuroinflammatory response / 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 / positive regulation of cerebellar granule cell precursor proliferation / lung vasculature development / exocytic vesicle / cerebellar granule cell precursor proliferation / positive regulation of myoblast proliferation / positive regulation of meiotic cell cycle / lung lobe morphogenesis / positive regulation of myelination / negative regulation of androgen receptor signaling pathway / cell activation / glial cell differentiation / positive regulation of developmental growth / prostate gland epithelium morphogenesis / positive regulation of calcineurin-NFAT signaling cascade / prostate gland growth / male sex determination / transmembrane receptor protein tyrosine kinase activator activity / type B pancreatic cell proliferation / mammary gland development / exocrine pancreas development / alphav-beta3 integrin-IGF-1-IGF1R complex / myoblast differentiation / cell surface receptor signaling pathway via STAT / regulation of nitric oxide biosynthetic process / positive regulation of Ras protein signal transduction / positive regulation of insulin-like growth factor receptor signaling pathway / positive regulation of smooth muscle cell migration / growth hormone receptor signaling pathway / positive regulation of DNA binding / adrenal gland development / negative regulation of interleukin-1 beta production / lung alveolus development / muscle organ development / cellular response to insulin-like growth factor stimulus / branching morphogenesis of an epithelial tube / positive regulation of cardiac muscle hypertrophy / androgen receptor signaling pathway / prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis / negative regulation of release of cytochrome c from mitochondria / type I pneumocyte differentiation / positive regulation of activated T cell proliferation / negative regulation of smooth muscle cell apoptotic process / inner ear development / negative regulation of amyloid-beta formation / myoblast proliferation / insulin receptor substrate binding / epithelial to mesenchymal transition / negative regulation of tumor necrosis factor production / blood vessel remodeling / Synthesis, secretion, and deacylation of Ghrelin / epidermis development / activation of protein kinase B activity / positive regulation of glycogen biosynthetic process / positive regulation of osteoblast differentiation / SHC-related events triggered by IGF1R / postsynaptic modulation of chemical synaptic transmission / phosphatidylinositol 3-kinase binding / positive regulation of vascular associated smooth muscle cell proliferation / negative regulation of MAPK cascade / insulin-like growth factor receptor binding / extrinsic apoptotic signaling pathway in absence of ligand / T-tubule / positive regulation of smooth muscle cell proliferation / 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 / animal organ morphogenesis / positive regulation of epithelial cell proliferation
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)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.3 Å
AuthorsLi, J. / Choi, E. / Yu, H.T. / Bai, X.C.
CitationJournal: Nat Commun / Year: 2019
Title: Structural basis of the activation of type 1 insulin-like growth factor receptor.
Authors: Jie Li / Eunhee Choi / Hongtao Yu / Xiao-Chen Bai /
Abstract: Type 1 insulin-like growth factor receptor (IGF1R) is a receptor tyrosine kinase that regulates cell growth and proliferation, and can be activated by IGF1, IGF2, and insulin. Here, we report the ...Type 1 insulin-like growth factor receptor (IGF1R) is a receptor tyrosine kinase that regulates cell growth and proliferation, and can be activated by IGF1, IGF2, and insulin. Here, we report the cryo-EM structure of full-length IGF1R-IGF1 complex in the active state. This structure reveals that only one IGF1 molecule binds the Γ-shaped asymmetric IGF1R dimer. The IGF1-binding site is formed by the L1 and CR domains of one IGF1R protomer and the α-CT and FnIII-1 domains of the other. The liganded α-CT forms a rigid beam-like structure with the unliganded α-CT, which hinders the conformational change of the unliganded α-CT required for binding of a second IGF1 molecule. We further identify an L1-FnIII-2 interaction that mediates the dimerization of membrane-proximal domains of IGF1R. This interaction is required for optimal receptor activation. Our study identifies a source of the negative cooperativity in IGF1 binding to IGF1R and reveals the structural basis of IGF1R activation.
History
DepositionJul 29, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 23, 2019Provider: repository / Type: Initial release
Revision 1.1Oct 30, 2024Group: Data collection / Database references / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / em_admin / pdbx_entry_details / pdbx_modification_feature
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _em_admin.last_update

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-20524
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Insulin-like growth factor 1 receptor
B: Insulin-like growth factor I
D: Insulin-like growth factor 1 receptor


Theoretical massNumber of molelcules
Total (without water)298,2243
Polymers298,2243
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: assay for oligomerization
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area7370 Å2
ΔGint-41 kcal/mol
Surface area85950 Å2

-
Components

#1: Protein Insulin-like growth factor 1 receptor / Insulin-like growth factor I receptor / IGF-I receptor


Mass: 145279.906 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Igf1r / Cell line (production host): HEK293 / Production host: Homo sapiens (human)
References: UniProt: Q60751, receptor protein-tyrosine kinase
#2: Protein Insulin-like growth factor I / IGF-I / Mechano growth factor / MGF / Somatomedin-C


Mass: 7663.752 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IGF1, IBP1 / Production host: Escherichia coli (E. coli) / References: UniProt: P05019
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

Component
IDNameTypeEntity IDParent-IDSource
1Full-length MmIGF1R-HsIGF1 complexCOMPLEXall0RECOMBINANT
2MmIGF1RCOMPLEX#11RECOMBINANT
3HsIGF1COMPLEX#21RECOMBINANT
Molecular weightValue: 0.336 MDa / Experimental value: NO
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
12Mus musculus (house mouse)10090
23Homo sapiens (human)9606
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-IDCell
12Homo sapiens (human)9606HEK293
23Escherichia coli (E. coli)562
Buffer solutionpH: 7.5
SpecimenConc.: 7 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportDetails: unspecified
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 %

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Cs: 2.7 mm / C2 aperture diameter: 70 µm / Alignment procedure: COMA FREE
Specimen holderCryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingAverage exposure time: 15 sec. / Electron dose: 50 e/Å2 / Film or detector model: GATAN K2 IS (4k x 4k)

-
Processing

SoftwareName: PHENIX / Version: 1.16_3549: / Classification: refinement
EM software
IDNameCategory
1RELIONparticle selection
2EPUimage acquisition
7Cootmodel fitting
9PHENIXmodel refinement
10RELIONinitial Euler assignment
11RELIONfinal Euler assignment
12RELIONclassification
13RELION3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 1431211
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 4.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 51573 / Symmetry type: POINT
Atomic model buildingProtocol: FLEXIBLE FIT / Space: REAL
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00713492
ELECTRON MICROSCOPYf_angle_d0.79918293
ELECTRON MICROSCOPYf_dihedral_angle_d6.9458090
ELECTRON MICROSCOPYf_chiral_restr0.051978
ELECTRON MICROSCOPYf_plane_restr0.0052372

+
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