Journal article

Structural Congruency of Ligand Binding to the Insulin and Insulin/Type 1 Insulin-like Growth Factor Hybrid Receptors

John G Menting, Callum F Lawrence, Geoffrey K-W Kong, Mai B Margetts, Colin W Ward, Michael C Lawrence

STRUCTURE | CELL PRESS | Published : 2015

Abstract

The homodimeric insulin and type 1 insulin-like growth factor receptors (IR and IGF-1R) share a common architecture and each can bind all three ligands within the family: insulin and insulin-like growth factors I and II (IGF-I and IFG-II). The receptor monomers also assemble as heterodimers, the primary ligand-binding sites of which each comprise the first leucine-rich repeat domain (L1) of one receptor type and an α-chain C-terminal segment (αCT) of the second receptor type. We present here crystal structures of IGF-I bound to such a hybrid primary binding site and of a ligand-free version of an IR αCT peptide bound to an IR L1 plus cysteine-rich domain construct (IR310.T). These structures..

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University of Melbourne Researchers

Grants

Awarded by Australian National Health and Medical Research Council (NHMRC)


Awarded by NHMRC Independent Research Institutes


Funding Acknowledgements

This work was supported by Australian National Health and Medical Research Council (NHMRC) Project Grants 1005896 and 1058233 and the Hazel and Pip Appel Fund (to M.C.L.); and NHMRC Independent Research Institutes Infrastructure Support Scheme Grant 361646 and Victorian State Government Operational Infrastructure Support Grant (to the Walter and Eliza Hall Institute). Diffraction data were obtained at the Australian Synchrotron (beamline MX2). We thank Dr. Louis Lu and the fermentation group at the CSIRO Manufacturing Flagship (Parkville, Australia) for large-scale mammalian cell culture. C.F.L. acknowledges an Australian Postgraduate Award.