Journal article
How ligand binds to the type 1 insulin-like growth factor receptor
Y Xu, GKW Kong, JG Menting, MB Margetts, CA Delaine, LM Jenkin, VV Kiselyov, P De Meyts, BE Forbes, MC Lawrence
Nature Communications | NATURE PUBLISHING GROUP | Published : 2018
Open access
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 struc..
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Funding Acknowledgements
This article is dedicated to Dr Colin Ward, our colleague who initiated the study but sadly passed away before its conclusion. The work was supported by grants APP1128456 and APP1128553 to M.C.L. and APP1069328 to B.E.F. from the Australian National Health and Medical Research Council (NHMRC) and made possible at WEHI through Victorian State Government Operational Infrastructure Support and the Australian NHMRC Independent Research Institutes Infrastructure Support Scheme. Diffraction data were collected at the Australian Synchrotron beamline MX2 and crystallization screening was conducted at the CSIRO Collaborative Crystallization Centre (Parkville, Australia). We thank Professor Kenneth Siddle (University of Cambridge) for providing the hybridoma cell lines from which the sequences of mAb 24-60 were determined. Figure 1a is adapted from Fig. 1e of ref. 8 (copyright 2016) with permission from Elsevier.