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

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

Edité par CCSD ; Elsevier (Cell Press) -

International audience. 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.

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