5UV8

Interleukin-3 Receptor Complex

Summary for 5UV8

• Entry DOI: 10.2210/pdb5uv8/pdb
• Descriptor: Interleukin-3 receptor subunit alpha, Interleukin-3, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: receptor, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 97324.76

Authors

Broughton, S.E.,Parker, M.W. (deposition date: 2017-02-19, release date: 2018-02-07, Last modification date: 2024-11-13)

Primary citation

Broughton, S.E.,Hercus, T.R.,Nero, T.L.,Kan, W.L.,Barry, E.F.,Dottore, M.,Cheung Tung Shing, K.S.,Morton, C.J.,Dhagat, U.,Hardy, M.P.,Wilson, N.J.,Downton, M.T.,Schieber, C.,Hughes, T.P.,Lopez, A.F.,Parker, M.W.
A dual role for the N-terminal domain of the IL-3 receptor in cell signalling.
Nat Commun, 9:386-386, 2018

PubMed 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.

PubMed: 29374162
DOI: 10.1038/s41467-017-02633-7

Experimental method

X-RAY DIFFRACTION (2.7 Å)