Extracellular complexes of the hematopoietic human and mouse CSF-1 receptor are driven by common assembly principles.
Structure. 2011-12-01; 19(12): 1762-1772
DOI: 10.1016/j.str.2011.10.012
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1. Structure. 2011 Dec 7;19(12):1762-72. doi: 10.1016/j.str.2011.10.012.
Extracellular complexes of the hematopoietic human and mouse CSF-1 receptor are
driven by common assembly principles.
Elegheert J(1), Desfosses A, Shkumatov AV, Wu X, Bracke N, Verstraete K, Van
Craenenbroeck K, Brooks BR, Svergun DI, Vergauwen B, Gutsche I, Savvides SN.
Author information:
(1)Unit for Structural Biology, Laboratory for Protein Biochemistry and
Biomolecular Engineering, Ghent University, K.L. Ledeganckstraat 35, 9000 Ghent,
Belgium.
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.
Copyright © 2011 Elsevier Ltd. All rights reserved.
DOI: 10.1016/j.str.2011.10.012
PMCID: PMC3260422
PMID: 22153499 [Indexed for MEDLINE]