Extracellular Complexes of the Hematopoietic Human and Mouse CSF-1 Receptor Are Driven by Common Assembly Principles

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• 作者：Jonathan Elegheert¹ ; Ambroise Desfosses³ ; Alexander  ; V. Shkumatov⁴ ; Xiongwu Wu⁵ ; Nathalie Bracke¹ ; Kenneth Verstraete¹ ; Kathleen Van  ; Craenenbroeck² ; Bernard  ; R. Brooks⁵ ; Dmitri  ; I. Svergun⁴ ; Bjorn Vergauwen¹ ; Irina Gutsche³ ;   ; ^{gutsche@embl.fr} ; Savvas  ; N. Savvides¹ ;   ; ^{savvas.savvides@ugent.be}
• 刊名：Structure
• 出版年：2011
• 出版时间：7 December 2011
• 年：2011
• 卷：19
• 期：12
• 页码：1762-1772
• 全文大小：1448 K

文摘

Summary

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.