Related ArticlesNMR characterization of the binding properties and conformation of glycosaminoglycans interacting with interleukin-10.
Glycobiology. 2014 Nov;24(11):1036-49
Authors: Künze G, Gehrcke JP, Pisabarro MT, Huster D
Abstract
The cytokine interleukin-10 (IL-10) is an important regulator of the host immune system with both pro- and anti-inflammatory functions. Glycosaminoglycans (GAGs) play a decisive role in the biology of many growth factors, e.g., for receptor binding or protection from proteolytic degradation. GAGs of the extracellular matrix inhibit IL-10 signaling, however, the molecular mechanism is so far unknown. Here, we studied the interaction between GAGs and IL-10 using a combination of nuclear magnetic resonance (NMR) spectroscopy and computer simulations. The binding region of a set of heparin and chondroitin sulfate GAG disaccharides with varying sulfation pattern were determined by saturation transfer difference (STD) NMR spectroscopy. From the initial growth rate of the STD amplification factor binding affinities were determined and KD values in the low millimolar to micromolar range were obtained. We observed the highest binding affinity to IL-10 with fully sulfated heparin; however, a hyaluronan hexasaccharide did not exhibit binding, which suggests that GAG sulfation is necessary for interaction with IL-10. For octasaccharides or longer GAGs, a cooperative binding behavior was observed, which could indicate simultaneous interaction with both dimer subunits of IL-10. Finally, structural information about the bound GAG was exemplarily obtained for a heparin tetrasaccharide fragment (?UA,2S-GlcNS,6S-IdoA,2S-GlcNS,6S) using transferred NOESY experiments, proton-proton scalar couplings and molecular dynamics simulations. The overall backbone conformation is only slightly changed in the presence of IL-10 and the conformational equilibrium between (1)C4 chair and (2)So skew-boat structure of the internal iduronic acid residue is preserved.
[NMR paper] Heparin-Binding Proteins (Chemokines and Defensins) and their Complexes with Glycosaminoglycans from the Solution NMR Perspective.
Heparin-Binding Proteins (Chemokines and Defensins) and their Complexes with Glycosaminoglycans from the Solution NMR Perspective.
Related Articles Heparin-Binding Proteins (Chemokines and Defensins) and their Complexes with Glycosaminoglycans from the Solution NMR Perspective.
Curr Protein Pept Sci. 2014 Aug 25;
Authors: Pomin VH
Abstract
This review paper aims at discussing the major recent achievements in the field of the heparin-binding proteins (HBPs), primarily chemokines and defensins, and their complexes with...
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[NMR paper] Solution NMR conformation of glycosaminoglycans.
Solution NMR conformation of glycosaminoglycans.
Related Articles Solution NMR conformation of glycosaminoglycans.
Prog Biophys Mol Biol. 2014 Feb 19;
Authors: Pomin VH
Abstract
Nuclear magnetic resonance (NMR) spectroscopy has been giving a pivotal contribution to the progress of glycomics, mostly by elucidating the structural, dynamical, conformational and intermolecular binding aspects of carbohydrates. Particularly in the field of conformation, NOE resonances, scalar couplings, residual dipolar couplings, and chemical shift...
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[NMR paper] Investigation of Lysine Side Chain Interactions of Interleukin-8 with Heparin and other Glycosaminoglycans Studied by a Methylation-NMR Approach.
Investigation of Lysine Side Chain Interactions of Interleukin-8 with Heparin and other Glycosaminoglycans Studied by a Methylation-NMR Approach.
Investigation of Lysine Side Chain Interactions of Interleukin-8 with Heparin and other Glycosaminoglycans Studied by a Methylation-NMR Approach.
Glycobiology. 2013 Aug 27;
Authors: Möbius K, Nordsieck K, Pichert A, Samsonov SA, Thomas L, Schiller J, Kalkhof S, Pisabarro MT, Beck-Sickinger AG, Huster D
Abstract
Although the interaction between interleukin-8 (IL-8) and glycosaminoglycans (GAG) is...
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08-29-2013 01:53 PM
[NMR paper] NMR dynamics-derived insights into the binding properties of a peptide interacting wi
NMR dynamics-derived insights into the binding properties of a peptide interacting with an SH2 domain.
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Biochemistry. 2005 Jan 18;44(2):694-703
Authors: Finerty PJ, Mittermaier AK, Muhandiram R, Kay LE, Forman-Kay JD
The signal transduction protein phospholipase C-gamma1 (PLC-gamma1) is activated when its C-terminal SH2 domain (PLCC) binds the phosphorylated Tyr-1021 site (pTyr-1021) in the beta-platelet-derived growth factor...
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[NMR paper] Direct determination of the interleukin-6 binding epitope of the interleukin-6 recept
Direct determination of the interleukin-6 binding epitope of the interleukin-6 receptor by NMR spectroscopy.
Related Articles Direct determination of the interleukin-6 binding epitope of the interleukin-6 receptor by NMR spectroscopy.
J Biol Chem. 2004 Jan 2;279(1):571-6
Authors: Schwantner A, Dingley AJ, Ozbek S, Rose-John S, Grötzinger J
All cytokines belonging to the interleukin-6 (IL-6)-type family of cytokines utilize receptors that have a modular build of several immunoglobulin-like and fibronectin type III-like domains. Characteristic...
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[NMR paper] Active conformations of glycosaminoglycans. NMR determination of the conformation of
Active conformations of glycosaminoglycans. NMR determination of the conformation of heparin sequences complexed with antithrombin and fibroblast growth factors in solution.
Related Articles Active conformations of glycosaminoglycans. NMR determination of the conformation of heparin sequences complexed with antithrombin and fibroblast growth factors in solution.
Semin Thromb Hemost. 2002 Aug;28(4):325-34
Authors: Hricovíni M, Guerrini M, Bisio A, Torri G, Naggi A, Casu B
Binding to proteins usually induces perturbation of nuclear magnetic...
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[NMR paper] Mapping the interacting regions between troponins T and C. Binding of TnT and TnI pep
Mapping the interacting regions between troponins T and C. Binding of TnT and TnI peptides to TnC and NMR mapping of the TnT-binding site on TnC.
Related Articles Mapping the interacting regions between troponins T and C. Binding of TnT and TnI peptides to TnC and NMR mapping of the TnT-binding site on TnC.
J Biol Chem. 2001 Sep 28;276(39):36606-12
Authors: Blumenschein TM, Tripet BP, Hodges RS, Sykes BD
Muscular contraction is triggered by an increase in calcium concentration, which is transmitted to the contractile proteins by the troponin...
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11-19-2010 08:44 PM
[NMR paper] NMR studies of the solution properties of recombinant murine interleukin-6.
NMR studies of the solution properties of recombinant murine interleukin-6.
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Biochim Biophys Acta. 1995 Jun 12;1249(2):189-203
Authors: Morton CJ, Bai H, Zhang JG, Hammacher A, Norton RS, Simpson RJ, Mabbutt BC
The effects of solvent, pH and temperature on the 1H-NMR spectra of recombinant murine interleukin-6 (IL-6) are described. Assignments made from two-dimensional homonuclear spectra are presented for resonances of the fifteen aromatic amino-acid...
NMR characterization of the binding properties and conformation of glycosaminoglycans interacting with interleukin-10.
Linear Mode
