Extracellular complexes of the hematopoietic human and mouse CSF-1 receptor are driven by common assembly principles.

Jonathan Elegheert (1) , Ambroise Desfosses (2) , Alexander V Shkumatov , Xiongwu Wu , Nathalie Bracke , Kenneth Verstraete (1) , Kathleen van Craenenbroeck , Bernard R Brooks , Dmitri I Svergun , Bjorn Vergauwen (1) , Irina Gutsche (3) , Savvas N Savvides (1)

1 Unit Struct Biol
2 Structural and Computational Biology Unit
3 UVHCI - Unit of Virus Host Cell Interactions = Biologie structurale des interactions entre virus et cellule hôte

The hematopoietic colony stimulating factor-1 receptor (CSF-1R or FMS) is essential for the cellular repertoire of the mammalian immune system. Here, we report a structural and mechanistic consensus for the assembly of human and mouse CSF-1:CSF-1R complexes. The EM structure of the complete extracellular assembly of the human CSF-1:CSF-1R complex reveals how receptor dimerization by CSF-1 invokes a ternary complex featuring extensive homotypic receptor contacts and striking structural plasticity at the extremities of the complex. Studies by small-angle X-ray scattering of unliganded hCSF-1R point to large domain rearrangements upon CSF-1 binding, and provide structural evidence for the relevance of receptor predimerization at the cell surface. Comparative structural and binding studies aiming to dissect the assembly principles of human and mouse CSF-1R complexes, including a quantification of the CSF-1/CSF-1R species cross-reactivity, show that bivalent cytokine binding to receptor coupled to ensuing receptor-receptor interactions are common denominators in extracellular complex formation.

Domaines: Biologie structurale [q-bio.BM]

Jonathan Elegheert, Ambroise Desfosses, Alexander V Shkumatov, Xiongwu Wu, Nathalie Bracke, et al.. Extracellular complexes of the hematopoietic human and mouse CSF-1 receptor are driven by common assembly principles.. Structure (London, England : 1993), 2011, 19 (12), pp.1762-72. ⟨hal-01243659⟩