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

Yibin Xu, Geoffrey K-W. Kong, John G. Menting, Mai B. Margetts, Carlie A. Delaine, Lauren M. Jenkin, Vladislav V. Kiselyov, Pierre De Meyts, Briony E. Forbes, Michael C. Lawrence

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84 Citations (Scopus)
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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.

Original languageEnglish
Article number821
Number of pages13
JournalNature Communications
Publication statusPublished - 26 Feb 2018


  • kinases
  • X-ray crystallography


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