4WRM

Structure of the human CSF-1:CSF-1R complex

Summary for 4WRM

• Entry DOI: 10.2210/pdb4wrm/pdb
• Related: 4WRL
• Descriptor: Macrophage colony-stimulating factor 1 receptor, Macrophage colony-stimulating factor 1 (2 entities in total)
• Functional Keywords: cytokine-cytokine receptor complex, cytokine/cytokine receptor
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 74478.83

Authors

Felix, J.,De Munck, S.,Elegheert, J.,Savvides, S.N. (deposition date: 2014-10-24, release date: 2015-08-12, Last modification date: 2024-11-13)

Primary citation

Felix, J.,De Munck, S.,Verstraete, K.,Meuris, L.,Callewaert, N.,Elegheert, J.,Savvides, S.N.
Structure and Assembly Mechanism of the Signaling Complex Mediated by Human CSF-1.
Structure, 23:1621-1631, 2015

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-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.

PubMed: 26235028
DOI: 10.1016/j.str.2015.06.019

Experimental method

X-RAY DIFFRACTION (6.853 Å)