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PDBsum entry 4wrm
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Cytokine/cytokine receptor
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PDB id
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4wrm
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References listed in PDB file
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Key reference
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Title
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Structure and assembly mechanism of the signaling complex mediated by human csf-1.
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Authors
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J.Felix,
S.De munck,
K.Verstraete,
L.Meuris,
N.Callewaert,
J.Elegheert,
S.N.Savvides.
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Ref.
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Structure, 2015,
23,
1621-1631.
[DOI no: ]
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PubMed id
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Abstract
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Human colony-stimulating factor 1 receptor (hCSF-1R) is unique among the
hematopoietic receptors because it is activated by two distinct cytokines, CSF-1
and interleukin-34 (IL-34). Despite ever-growing insights into the central role
of hCSF-1R signaling in innate and adaptive immunity, inflammatory diseases, and
cancer, the structural basis of the functional dichotomy of hCSF-1R has remained
elusive. Here, we report crystal structures of ternary complexes between hCSF-1
and hCSF-1R, including their complete extracellular assembly, and propose a
mechanism for the cooperative human CSF-1:CSF-1R complex that relies on the
adoption by dimeric hCSF-1 of an active conformational state and homotypic
receptor interactions. Furthermore, we trace the cytokine-binding duality of
hCSF-1R to a limited set of conserved interactions mediated by functionally
equivalent residues on CSF-1 and IL-34 that play into the geometric requirements
of hCSF-1R activation, and map the possible mechanistic consequences of somatic
mutations in hCSF-1R associated with cancer.
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