Journal article
Conformational Changes in the GM-CSF Receptor Suggest a Molecular Mechanism for Affinity Conversion and Receptor Signaling
SE Broughton, TR Hercus, TL Nero, M Dottore, BJ McClure, U Dhagat, H Taing, MA Gorman, J King-Scott, AF Lopez, MW Parker
Structure | CELL PRESS | Published : 2016
Abstract
The GM-CSF, IL-3, and IL-5 receptors constitute the βc family, playing important roles in inflammation, autoimmunity, and cancer. Typical of heterodimeric type I cytokine receptors, signaling requires recruitment of the shared subunit to the initial cytokine:α subunit binary complex through an affinity conversion mechanism. This critical process is poorly understood due to the paucity of crystal structures of both binary and ternary receptor complexes for the same cytokine. We have now solved the structure of the binary GM-CSF:GMRα complex at 2.8-Å resolution and compared it with the structure of the ternary complex, revealing distinct conformational changes. Guided by these differences we p..
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Funding Acknowledgements
This research was partly undertaken on the MX2 beamline at the Australian Synchrotron, Victoria, Australia, and we thank the beamline staff for their assistance. We thank and acknowledge the use of the CSIRO Collaborative Crystallisation Centre (C3), Melbourne, Australia for our initial crystallization studies. We thank Dene Littler for his contributions to the structural studies, Joanna Woodcock for helpful discussions, and Anna Sapa for technical assistance. This work was supported by grants from the National Health and Medical Research Council of Australia (NHMRC) to T.R.H., M.W.P., and A.F.L., and from the Australian Cancer Research Foundation to M.W.P. Funding from the Victorian Government Operational Infrastructure Support Scheme to St Vincent's Institute is acknowledged. S.E.B. is a Postdoctoral Fellow supported by the Leukaemia Foundation. U.D. and M.W.P. are NHMRC Postdoctoral and Research Fellows, respectively.