@article{2f16f4018bf24091b48de377bfe1918d,
title = "The Structure of the GM-CSF Receptor Complex Reveals a Distinct Mode of Cytokine Receptor Activation",
abstract = "Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that controls the production and function of blood cells, is deregulated in clinical conditions such as rheumatoid arthritis and leukemia, yet offers therapeutic value for other diseases. Its receptors are heterodimers consisting of a ligand-specific α subunit and a βc subunit that is shared with the interleukin (IL)-3 and IL-5 receptors. How signaling is initiated remains an enigma. We report here the crystal structure of the human GM-CSF/GM-CSF receptor ternary complex and its assembly into an unexpected dodecamer or higher-order complex. Importantly, mutagenesis of the GM-CSF receptor at the dodecamer interface and functional studies reveal that dodecamer formation is required for receptor activation and signaling. This unusual form of receptor assembly likely applies also to IL-3 and IL-5 receptors, providing a structural basis for understanding their mechanism of activation and for the development of therapeutics.",
author = "Guido Hansen and Hercus, {Timothy R.} and McClure, {Barbara J.} and Stomski, {Frank C.} and Mara Dottore and Jason Powell and Hayley Ramshaw and Woodcock, {Joanna M.} and Yibin Xu and Mark Guthridge and McKinstry, {William J.} and Lopez, {Angel F.} and Parker, {Michael W.}",
note = "Funding Information: We thank Jamie Rossjohn for his contributions during the early stages of this work, Richard D'Andrea for the pEQEco plasmid, Chris Bagley for helpful discussions, and Rebecca Krake and Anna Sapa for technical assistance. We thank Harry Tong and other staff at BioCARS for their help during our visit to the Advanced Photon Source (APS). Access to BioCARS was provided by the Australian Synchrotron Research Program funded by the Commonwealth of Australia. BioCARS is supported by the U.S. National Institutes of Health, National Center for Research Resources. APS is supported by the U.S. Department of Energy. This work was supported by grants from the National Health and Medical Research Council of Australia (NHMRC), the National Institutes of Health (RO1-AI50744-02), and the Australian Cancer Research Foundation. H.R. is a Peter Nelson Leukaemia Research Fund Senior Research Fellow. M.W.P. is an Australian Research Council Federation Fellow and an NHMRC Honorary Fellow. ",
year = "2008",
month = aug,
day = "8",
doi = "10.1016/j.cell.2008.05.053",
language = "English",
volume = "134",
pages = "496--507",
journal = "Cell",
issn = "0092-8674",
number = "3",
}
