5U8Q

Structure of the ectodomain of the human Type 1 insulin-like growth factor receptor in complex with IGF-I


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.27 Å
  • R-Value Free: 0.303 
  • R-Value Work: 0.260 
  • R-Value Observed: 0.262 

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This is version 2.1 of the entry. See complete history


Literature

How ligand binds to the type 1 insulin-like growth factor receptor.

Xu, Y.Kong, G.K.Menting, J.G.Margetts, M.B.Delaine, C.A.Jenkin, L.M.Kiselyov, V.V.De Meyts, P.Forbes, B.E.Lawrence, M.C.

(2018) Nat Commun 9: 821-821

  • DOI: https://doi.org/10.1038/s41467-018-03219-7
  • Primary Citation of Related Structures:  
    5U8Q, 5U8R

  • PubMed Abstract: 

    Human type 1 insulin-like growth factor receptor is a homodimeric receptor tyrosine kinase that signals into pathways directing normal cellular growth, differentiation and proliferation, with aberrant signalling implicated in cancer. Insulin-like growth factor binding is understood to relax conformational restraints within the homodimer, initiating transphosphorylation of the tyrosine kinase domains. However, no three-dimensional structures exist for the receptor ectodomain to inform atomic-level understanding of these events. Here, we present crystal structures of the ectodomain in apo form and in complex with insulin-like growth factor I, the latter obtained by crystal soaking. These structures not only provide a wealth of detail of the growth factor interaction with the receptor's primary ligand-binding site but also indicate that ligand binding separates receptor domains by a mechanism of induced fit. Our findings are of importance to the design of agents targeting IGF-1R and its partner protein, the human insulin receptor.


  • Organizational Affiliation

    The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC, 3052, Australia.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Insulin-like growth factor 1 receptor885Homo sapiensMutation(s): 0 
Gene Names: IGF1R
EC: 2.7.10.1
UniProt & NIH Common Fund Data Resources
Find proteins for P08069 (Homo sapiens)
Explore P08069 
Go to UniProtKB:  P08069
PHAROS:  P08069
GTEx:  ENSG00000140443 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP08069
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Insulin-like growth factor I70Homo sapiensMutation(s): 0 
Gene Names: IGF1IBP1
UniProt & NIH Common Fund Data Resources
Find proteins for P05019 (Homo sapiens)
Explore P05019 
Go to UniProtKB:  P05019
PHAROS:  P05019
GTEx:  ENSG00000017427 
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UniProt GroupP05019
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Fv 24-60 heavy chainC [auth H]126Mus musculusMutation(s): 0 
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
Fv 24-60 light chainD [auth L]108Mus musculusMutation(s): 0 
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 5
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranoseE [auth C],
G [auth E]
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Entity ID: 6
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-4)-alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranoseF [auth D]4N-Glycosylation
Glycosylation Resources
GlyTouCan:  G81874LD
GlyCosmos:  G81874LD
GlyGen:  G81874LD
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.27 Å
  • R-Value Free: 0.303 
  • R-Value Work: 0.260 
  • R-Value Observed: 0.262 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 88.69α = 90
b = 197.66β = 90
c = 117.65γ = 90
Software Package:
Software NamePurpose
phenix.refinerefinement
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2018-02-28
    Type: Initial release
  • Version 1.1: 2018-03-14
    Changes: Database references
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Structure summary
  • Version 2.1: 2023-10-04
    Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary