Human IL-34 and CSF-1 Establish Structurally Similar Extracellular Assemblies with Their Common Hematopoietic Receptor

wim — Tue, 26 Feb 2013 10:49:48 +0000

J. Felix, J. Elegheert, I. Gutsche, A. Shkumatov, Y. Wen, N. Bracke, E. Pannecoucke, I. Vandenberghe, B. Devreese, D.I. Svergun, E. Pauwels, B. Vergauwen, S.N. Savvides

Structure

21 (4), 528-539

2013

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.

DOI

http://dx.doi.org/10.1016/j.str.2013.01.018

Private attachment

13_Structure_21(4)528_Felix.pdf

Study of structure-function relationships in interleukin 34, a novel cytokine

ewald — Mon, 27 Feb 2012 22:36:51 +0000

J. Felix, J. Elegheert, N. Bracke, A. Shkumatov, E. Pauwels, S.N. Savvides

Poster

Conference / event / venue

2nd Belgian Biophysical Society Young Scientist Day

Ghent Belgium

Tuesday, 31 May, 2011

Molecular modeling of flavin ring plasticity: in-silico mutation of an Old Yellow Enzyme

wim — Fri, 26 Aug 2011 13:05:22 +0000

E. Pauwels, J. Elegheert, M. Waroquier, S.N. Savvides

Talk

Conference / event / venue

2nd Belgian Biophysical Society Young Scientist Day

Ghent, Belgium

Tuesday, 31 May, 2011

Center for Molecular Modeling - J. Elegheert

Human IL-34 and CSF-1 Establish Structurally Similar Extracellular Assemblies with Their Common Hematopoietic Receptor

Abstract

DOI

Private attachment

Study of structure-function relationships in interleukin 34, a novel cytokine

Conference / event / venue

Molecular modeling of flavin ring plasticity: in-silico mutation of an Old Yellow Enzyme

Conference / event / venue