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Structural insights into the interaction between a potent anti-inflammatory protein, vCCI, and the human CC chemokine, Eotaxin-1.
J Biol Chem. 2014 Jan 30;
Authors: Kuo NW, Gao YG, Schill MS, Isern N, Dupureur CM, Liwang PJ
Abstract
Chemokines play important roles in the immune system, not only recruiting leukocytes to the site of infection and inflammation but also guiding cell homing and cell development. The soluble poxvirus-encoded protein vCCI, a CC chemokine inhibitor, can bind to human CC chemokines tightly to impair the host immune defense. This protein has no known homologs in eukaryotes, and may represent a potent method to stop inflammation. Previously, our structure of the vCCI:MIP-1? complex indicated that vCCI uses negatively charged residues in ?-sheet II to interact with positively charged residues in the MIP-1? N-terminus,20’s region and 40’s loop. However, the interactions between vCCI and other CC chemokines have not yet been fully explored. Here, we used NMR and fluorescence anisotropy to study the interaction between vCCI and eotaxin-1 (CCL11), a CC chemokine that is an important factor in the asthma response. NMR results reveal that the binding pattern is very similar to the vCCI:MIP-1? complex, and suggest that electrostatic interactions provide a major contribution to binding. Fluorescence anisotropy results on variants of eotaxin-1 further confirm the critical roles of the charged residues in eotaxin. In addition, the binding affinity between vCCI and other wild type CC chemokines, MCP-1, MIP-1? and RANTES, were determined as 1.09 nM, 1.16 nM, and 0.22 nM, respectively. To our knowledge, this is the first work quantitatively measuring the binding affinity between vCCI and different CC chemokines.
PMID: 24482230 [PubMed – as supplied by publisher]
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