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PDBsum entry 5uwc
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Signaling protein
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PDB id
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5uwc
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References listed in PDB file
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Key reference
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Title
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A dual role for the n-Terminal domain of the il-3 receptor in cell signalling.
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Authors
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S.E.Broughton,
T.R.Hercus,
T.L.Nero,
W.L.Kan,
E.F.Barry,
M.Dottore,
K.S.Cheung tung shing,
C.J.Morton,
U.Dhagat,
M.P.Hardy,
N.J.Wilson,
M.T.Downton,
C.Schieber,
T.P.Hughes,
A.F.Lopez,
M.W.Parker.
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Ref.
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Nat Commun, 2018,
9,
386.
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PubMed id
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Abstract
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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.
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