| Title: | A dual role for the N-terminal domain of the IL-3 receptor in cell signalling |
| Authors: | Broughton, SE Hercus, TR Nero, TL Kan, WL Barry, EF Dottore, M Shing, KSCT Morton, CJ Dhagat, U Hardy, MP Wilson, NJ Downton, MT Schieber, C Hughes, TP Lopez, AF Parker, MW |
| Issue Year: | 2018 |
| Publisher | NATURE PUBLISHING GROUP |
| Series | Nat. Commun.: |
| 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 alpha-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 IL3R alpha 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 IL3R alpha 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. |
| URI: | https://publications.svi.edu.au/publications/4644 |
| Other Identifiers | 10.1038/s41467-017-02633-7 |
| Publication type | Article |