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

Nat Commun. 2018 Feb 26;9(1):821.

PMID: 29483580

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248141	Insulin-like Growth Factor-I human			Price