Journal
STRUCTURE
Volume 23, Issue 9, Pages 1621-1631Publisher
CELL PRESS
DOI: 10.1016/j.str.2015.06.019
Keywords
-
Funding
- FWO (Belgium)
- FWO [G0597.10, G0643.07N, G0B7912N, G.0.541.08.N.10]
- Hercules Foundation (Belgium) [AUGE-11-029]
- Ghent University Industrial Research Fund Advanced Grant [041]
- VIB (Belgium)
Ask authors/readers for more resources
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 evergrowing 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available