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Title | Structure and Assembly Mechanism of the Signaling Complex Mediated by Human CSF-1. |
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Journal, issue, pages | Structure, Vol. 23, Issue 9, Page 1621-1631, Year 2015 |
Publish date | Sep 1, 2015 |
![]() | Jan Felix / Steven De Munck / Kenneth Verstraete / Leander Meuris / Nico Callewaert / Jonathan Elegheert / Savvas N Savvides / ![]() |
PubMed Abstract | 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- ...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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Methods | SAS (X-ray synchrotron) / X-ray diffraction |
Resolution | 2.802 - 6.853 Å |
Structure data | ![]() SASDAR6: ![]() PDB-4wrl: ![]() PDB-4wrm: |
Chemicals | ![]() ChemComp-SIA: ![]() ChemComp-NAG: |
Source |
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![]() | CYTOKINE/CYTOKINE RECEPTOR / cytokine-cytokine receptor complex |