title: Extracellular complexes of the hematopoietic human and mouse CSF-1 receptor are driven by common assembly principles.
abstract: 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.
authors.affiliation: Unit for Structural Biology, Laboratory for Protein Biochemistry and Biomolecular Engineering, Ghent University, K.L. Ledeganckstraat 35, 9000 Ghent, Belgium.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Elegheert
authors.forename: Ambroise
authors.initials: A
authors.lastname: Desfosses
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Shkumatov
authors.forename: Xiongwu
authors.initials: X
authors.lastname: Wu
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bracke
authors.forename: Kenneth
authors.initials: K
authors.lastname: Verstraete
authors.forename: Kathleen
authors.initials: K
authors.lastname: Van Craenenbroeck
authors.forename: Bernard R
authors.initials: BR
authors.lastname: Brooks
authors.forename: Dmitri I
authors.initials: DI
authors.lastname: Svergun
authors.forename: Bjorn
authors.initials: B
authors.lastname: Vergauwen
authors.forename: Irina
authors.initials: I
authors.lastname: Gutsche
authors.forename: Savvas N
authors.initials: SN
authors.lastname: Savvides
mesh_terms: D000818:Animals; D001665:Binding Sites; D006413:Hematopoietic System; D006801:Humans; D008024:Ligands; D016173:Macrophage Colony-Stimulating Factor / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008854:Microscopy, Electron; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D008024:Ligands; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor