Structural Insights into the Interaction between a Potent Anti-inflammatory Protein, Viral CC Chemokine Inhibitor (vCCI), and the Human CC Chemokine, Eotaxin-1

	Structural Insights into the Interaction between a Potent Anti-inflammatory Protein, Viral CC Chemokine Inhibitor (vCCI), and the Human CC Chemokine, Eotaxin-1
	Kuo, NW; Gao, YG; Schill, MS; Isern, N; Dupureur, CM; LiWang, PJ
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2014
卷号	289 期号:10 页码:6592-6603
关键词	Biophysics Chemokines Molecular Docking NMR Protein-Protein Interactions Anti-inflammatory Protein Chemokine-binding Protein Eotaxin Fluorescence Anisotropy vCCI
通讯作者	LiWang, PJ (reprint author), Univ Calif, Dept Mol Cell Biol, 5200 N Lake Rd, Merced, CA 95343 USA.,pliwang@ucmerced.edu
英文摘要	Background: The mechanism used by viral protein vCCI to tightly bind to many CC chemokines is not known. Results: Specific positively charged residues in the chemokine eotaxin-1 mediate binding to vCCI. Conclusion: Basic residues in the chemokine each provide incremental affinity for vCCI. Significance: This work shows how vCCI can bind a variety of CC chemokines. 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 viral CC chemokine inhibitor (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 vCCIMIP-1 (macrophage inflammatory protein-1) complex indicated that vCCI uses negatively charged residues in -sheet II to interact with positively charged residues in the MIP-1 N terminus, 20s region and 40s 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 vCCIMIP-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-1. In addition, the binding affinity between vCCI and other wild type CC chemokines, MCP-1 (monocyte chemoattractant protein-1), MIP-1, and RANTES (regulated on activation normal T cell expressed and secreted), were determined as 1.1, 1.2, and 0.22 nm, respectively. To our knowledge, this is the first work quantitatively measuring the binding affinity between vCCI and multiple CC chemokines.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	TRIPLE-RESONANCE EXPERIMENTS ; BINDING-PROTEIN ; VACCINIA VIRUS ; DECOY RECEPTOR ; CRYSTAL-STRUCTURE ; WEB SERVER ; INFLAMMATION ; RECOGNITION ; BLOCKADE ; DETERMINANTS
收录类别	SCI
语种	英语
WOS记录号	WOS:000332389400024
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/238]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Kuo, NW,Gao, YG,Schill, MS,et al. Structural Insights into the Interaction between a Potent Anti-inflammatory Protein, Viral CC Chemokine Inhibitor (vCCI), and the Human CC Chemokine, Eotaxin-1[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2014,289(10):6592-6603.
APA	Kuo, NW,Gao, YG,Schill, MS,Isern, N,Dupureur, CM,&LiWang, PJ.(2014).Structural Insights into the Interaction between a Potent Anti-inflammatory Protein, Viral CC Chemokine Inhibitor (vCCI), and the Human CC Chemokine, Eotaxin-1.JOURNAL OF BIOLOGICAL CHEMISTRY,289(10),6592-6603.
MLA	Kuo, NW,et al."Structural Insights into the Interaction between a Potent Anti-inflammatory Protein, Viral CC Chemokine Inhibitor (vCCI), and the Human CC Chemokine, Eotaxin-1".JOURNAL OF BIOLOGICAL CHEMISTRY 289.10(2014):6592-6603.