Journal article
How insulin-like growth factor I binds to a hybrid insulin receptor type 1 insulin-like growth factor receptor
Y Xu, MB Margetts, H Venugopal, JG Menting, NS Kirk, TI Croll, C Delaine, BE Forbes, MC Lawrence
Structure | Published : 2022
Open access
Abstract
Monomers of the insulin receptor and type 1 insulin-like growth factor receptor (IGF-1R) can combine stochastically to form heterodimeric hybrid receptors. These hybrid receptors display ligand binding and signaling properties that differ from those of the homodimeric receptors. Here, we describe the cryoelectron microscopy structure of such a hybrid receptor in complex with insulin-like growth factor I (IGF-I). The structure (ca. 3.7 Å resolution) displays a single IGF-I ligand, bound in a similar fashion to that seen for IGFs in complex with IGF-1R. The IGF-I ligand engages the first leucine-rich-repeat domain and cysteine-rich region of the IGF-1R monomer (rather than those of the insulin..
View full abstractGrants
Awarded by Wellcome Trust
Funding Acknowledgements
M.C.L. acknowledges financial support from the Australian National Health and Medical Research Council (NHMRC) Project Grant APP1128553; his institute receives Victorian State Government Operational Infrastructure Support and funding from the Australian NHMRC Independent Research Institutes Infrastructure Support Scheme. The authors acknowledge the use of instruments and assistance at the Monash Ramaciotti Centre for Cryo-Electron Microscopy, a Node of Microscopy Australia. This research used equipment funded by Australian Research Council grant LE120100090. T.I.C. is supported by the Wellcome Trust Principal Research Fellowship of Prof. Randy Read (grant number 209407/Z/17/Z). This research was funded in whole, or in part, by the Wellcome Trust grant number 209407/Z/17/Z. For the purpose of open access, the author has applied a CC BY public copyright license to any author-accepted manuscript version arising from this submission. The authors thank Prof. Ken Siddle (University of Cambridge, UK) for providing the hybridomas expressing mAb 18-44 and Dr. Oliver Clarke (Columbia University, USA) for advice regarding cryo-EM software.