The N-terminal domain of CCL21 reconstitutes high affinity binding, G protein activation, and chemotactic activity, to the C-terminal domain of CCL19

被引:20
作者
Ott, Thomas R.
Lio, Francisco M.
Olshefski, Dennis
Liu, Xin-Jun
Ling, Nicholas
Struthers, R. Scott [1 ]
机构
[1] Neurocrine Biosci, Dept Endocrinol, San Diego, CA 92130 USA
[2] Neurocrine Biosci, Dept Peptide Chem, San Diego, CA 92130 USA
关键词
chemokine; chemokine receptors; CCR7; CCL19; CCL21;
D O I
10.1016/j.bbrc.2006.07.165
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
CC chemokine receptor 7 (CCR7), which regulates the trafficking of leucocytes to the secondary lymphoid organs, has two endogenous chemokine ligands: CCL19 and CCL21. Although both ligands possess similar affinities for the receptor and similar abilities to promote G protein activation and chemotaxis, they share only 25% sequence identity. Here, we show that substituting N-terminal six amino acids of CCL21 (SDGGAQ) for the corresponding N-terminal domain of CCL19 (GTNDAE) results in a chimeric chemokine that exhibits high affinity binding and G protein activation of CCR7. These data demonstrate that despite dissimilar sequences, the amino terminal hexapeptide of these two chemokines is capable of performing similar roles resulting in receptor activation. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:1089 / 1093
页数:5
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