5uwc | pdb_00005uwc
Cytokine-receptor complex
Structural highlights
Function[IL3RA_HUMAN] This is a receptor for interleukin-3. [IL3_HUMAN] Granulocyte/macrophage colony-stimulating factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and the monocytes-macrophages. This CSF induces granulocytes, macrophages, mast cells, stem cells, erythroid cells, eosinophils and megakaryocytes. Publication Abstract from PubMedThe 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 IL3Ralpha 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 IL3Ralpha 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. A dual role for the N-terminal domain of the IL-3 receptor in cell signalling.,Broughton SE, Hercus TR, Nero TL, Kan WL, Barry EF, Dottore M, Cheung Tung Shing KS, Morton CJ, Dhagat U, Hardy MP, Wilson NJ, Downton MT, Schieber C, Hughes TP, Lopez AF, Parker MW Nat Commun. 2018 Jan 26;9(1):386. doi: 10.1038/s41467-017-02633-7. PMID:29374162[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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