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Human IL-34 and CSF-1 establish structurally similar extracellular assemblies with their common hematopoietic receptor

Jan Félix (UGent) , Jonathan Elegheert (UGent) , Irina Gutsche, Alexander Shkumatov, Yurong Wen (UGent) , Nathalie Bracke (UGent) , Erwin Pannecoucke (UGent) , Isabel Vandenberghe (UGent) , Bart Devreese (UGent) , Dmitri Svergun, et al.
(2013) STRUCTURE. 21(4). p.528-539
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Abstract
The discovery that hematopoietic human colony stimulating factor-1 receptor (CSF-1R) can be activated by two distinct cognate cytokines, colony stimulating factor-1 (CSF-1) and interleukin-34 (IL-34), created puzzling scenarios for the two possible signaling complexes. We here employ a hybrid structural approach based on small-angle X-ray scattering (SAXS) and negative-stain EM to reveal that bivalent binding of human IL-34 to CSF-1R leads to an extracellular assembly hallmarked by striking similarities to the CSF-1:CSF-1R complex, including homotypic receptor-receptor interactions. Thus, IL-34 and CSF-1 have evolved to exploit the geometric requirements of CSF-1R activation. Our models include N-linked oligomannose glycans derived from a systematic approach resulting in the accurate fitting of glycosylated models to the SAXS data. We further show that the C-terminal region of IL-34 is heavily glycosylated and that it can be proteolytically cleaved from the IL-34:hCSF-1R complex, providing insights into its role in the functional nonredundancy of IL-34 and CSF-1.
Keywords
LANGERHANS CELLS, DISORDERED REGIONS, BIOLOGICAL MACROMOLECULES, ELECTRON-MICROSCOPY, MOLECULAR-DYNAMICS, TYROSINE KINASES, STIMULATING FACTOR-I, O-LINKED GLYCOSYLATION, RAY SOLUTION SCATTERING, SMALL-ANGLE SCATTERING

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Chicago
Félix, Jan, Jonathan Elegheert, Irina Gutsche, Alexander Shkumatov, Yurong Wen, Nathalie Bracke, Erwin Pannecoucke, et al. 2013. “Human IL-34 and CSF-1 Establish Structurally Similar Extracellular Assemblies with Their Common Hematopoietic Receptor.” Structure 21 (4): 528–539.
APA
Félix, J., Elegheert, J., Gutsche, I., Shkumatov, A., Wen, Y., Bracke, N., Pannecoucke, E., et al. (2013). Human IL-34 and CSF-1 establish structurally similar extracellular assemblies with their common hematopoietic receptor. STRUCTURE, 21(4), 528–539.
Vancouver
1.
Félix J, Elegheert J, Gutsche I, Shkumatov A, Wen Y, Bracke N, et al. Human IL-34 and CSF-1 establish structurally similar extracellular assemblies with their common hematopoietic receptor. STRUCTURE. 2013;21(4):528–39.
MLA
Félix, Jan, Jonathan Elegheert, Irina Gutsche, et al. “Human IL-34 and CSF-1 Establish Structurally Similar Extracellular Assemblies with Their Common Hematopoietic Receptor.” STRUCTURE 21.4 (2013): 528–539. Print.
@article{4214611,
  abstract     = {The discovery that hematopoietic human colony stimulating factor-1 receptor (CSF-1R) can be activated by two distinct cognate cytokines, colony stimulating factor-1 (CSF-1) and interleukin-34 (IL-34), created puzzling scenarios for the two possible signaling complexes. We here employ a hybrid structural approach based on small-angle X-ray scattering (SAXS) and negative-stain EM to reveal that bivalent binding of human IL-34 to CSF-1R leads to an extracellular assembly hallmarked by striking similarities to the CSF-1:CSF-1R complex, including homotypic receptor-receptor interactions. Thus, IL-34 and CSF-1 have evolved to exploit the geometric requirements of CSF-1R activation. Our models include N-linked oligomannose glycans derived from a systematic approach resulting in the accurate fitting of glycosylated models to the SAXS data. We further show that the C-terminal region of IL-34 is heavily glycosylated and that it can be proteolytically cleaved from the IL-34:hCSF-1R complex, providing insights into its role in the functional nonredundancy of IL-34 and CSF-1.},
  author       = {F{\'e}lix, Jan and Elegheert, Jonathan and Gutsche, Irina and Shkumatov, Alexander and Wen, Yurong and Bracke, Nathalie and Pannecoucke, Erwin and Vandenberghe, Isabel and Devreese, Bart and Svergun, Dmitri and Pauwels, Ewald and Vergauwen, Bjorn and Savvides, Savvas},
  issn         = {0969-2126},
  journal      = {STRUCTURE},
  language     = {eng},
  number       = {4},
  pages        = {528--539},
  title        = {Human IL-34 and CSF-1 establish structurally similar extracellular assemblies with their common hematopoietic receptor},
  url          = {http://dx.doi.org/10.1016/j.str.2013.01.018},
  volume       = {21},
  year         = {2013},
}
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