Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/116606
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Type: Journal article
Title: A dual role for the N-terminal domain of the IL-3 receptor in cell signalling
Author: Broughton, S.
Hercus, T.
Nero, T.
Kan, W.
Barry, E.
Dottore, M.
Cheung Tung Shing, K.
Morton, C.
Dhagat, U.
Hardy, M.
Wilson, N.
Downton, M.
Schieber, C.
Hughes, T.
Lopez, A.
Parker, M.
Citation: Nature Communications, 2018; 9(1):386-1-386-15
Publisher: Nature Publishing Group
Issue Date: 2018
ISSN: 2041-1723
2041-1723
Statement of
Responsibility: 
Sophie E. Broughton, Timothy R. Hercus, Tracy L. Nero, Winnie L. Kan ... Timothy P. Hughes, Angel F. Lopez ... et al.
Abstract: The interleukin-3 (IL-3) receptor is a cell-surface heterodimer that links the haemopoietic, vascular and immune systems and is overexpressed in acute and chronic myeloid leukaemia progenitor cells. It belongs to the type I cytokine receptor family in which the α-subunits consist of two fibronectin III-like domains that bind cytokine, and a third, evolutionarily unrelated and topologically conserved, N-terminal domain (NTD) with unknown function. Here we show by crystallography that, while the NTD of IL3Rα is highly mobile in the presence of IL-3, it becomes surprisingly rigid in the presence of IL-3 K116W. Mutagenesis, biochemical and functional studies show that the NTD of IL3Rα regulates IL-3 binding and signalling and reveal an unexpected role in preventing spontaneous receptor dimerisation. Our work identifies a dual role for the NTD in this cytokine receptor family, protecting against inappropriate signalling and dynamically regulating cytokine receptor binding and function.
Keywords: Cercopithecus aethiops
Rights: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
DOI: 10.1038/s41467-017-02633-7
Appears in Collections:Aurora harvest 3
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