Center for Molecular Modeling - J. Felix

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

An REMD and QM/MM study into the sequence effect on asparagine deamidation

wim — Tue, 19 Jun 2012 06:49:27 +0000

E. Pauwels, S.L. Moors, J. Felix, S.N. Savvides, M. Waroquier, V. Van Speybroeck, S. Catak

p. 9-10

Talk

Conference / event / venue

Enhancing Organocatalysis by Joining Advanced Theorectical and Experimental Approches

Lugano, Zwitseland

Wednesday, 13 June, 2012 to Friday, 15 June, 2012

Abstract (private)

2012 Abstract_CECAM_Lugano.pdf

Effect of the (n +1) residue on peptide deamidation

catak — Sat, 21 Apr 2012 11:22:18 +0000

S. Catak, J. Felix, V. Van Speybroeck, M. Waroquier, E. Pauwels

Talk

Conference / event / venue

ACS Spring 2012 National Meeting & Exposition

San Diego, USA

Sunday, 25 March, 2012 to Thursday, 29 March, 2012

Abstract (private)

ACS abstract.pdf

Conference reference

ACS Spring 2012

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

Peptide Deamidation: Effect of Neighboring Residues

wim — Fri, 23 Sep 2011 07:33:06 +0000

S. Catak, J. Felix, S.N. Savvides, V. Van Speybroeck, M. Waroquier, E. Pauwels

p. 53

Poster

Conference / event / venue

Conference on Molecular Simulations in Biosystems and Material Science (SimBioMa)

Konstanz, Germany

Wednesday, 28 September, 2011 to Saturday, 1 October, 2011

Abstract

2011 SIMBIOMA SCatak.pdf

Conference reference

SimBioMa 2011

A combined computational-experimental approach to study structure-function relationships in a novel cytokine

wim — Wed, 24 Aug 2011 12:59:00 +0000

J. Felix

Master of Science in Biochemistry and Biotechnology

2010

Supervisors

Dr. Ewald Pauwels, Prof. Dr. Savvas Savvides

Jan Felix

wim — Tue, 23 Aug 2011 13:35:02 +0000

Master Biochem/Biotech Jan Felix has been awarded the Ablynx (TM) prize 2009-2010 for his master thesis "A combined computational-experimental approach to study structure-function relationships in a novel cytokine", supervised by Dr. Ewald Pauwels (CMM) and Prof. Dr. Savvas Savvides.