How ligand binds to the type 1 insulin-like growth factor receptor
- Author(s)
- Xu, Y; Kong, GK; Menting, JG; Margetts, MB; Delaine, CA; Jenkin, LM; Kiselyov, VV; De Meyts, P; Forbes, BE; Lawrence, MC;
- Details
- Publication Year 2018-02-26,Volume 9,Issue #1,Page 821
- Journal Title
- Nature Communications
- Publication Type
- Journal Article
- 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.
- Publisher
- Springer Nature
- Research Division(s)
- Structural Biology
- PubMed ID
- 29483580
- Publisher's Version
- https://doi.org/10.1038/s41467-018-03219-7
- Open Access at Publisher's Site
https://doi.org/10.1038/s41467-018-03219-7- NHMRC Grants
- NHMRC/1128553,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2018-07-09 02:07:34
Last Modified: 2018-07-09 02:23:55