4.5 Article

Cathepsin X cleavage of the β2 integrin regulates talin-binding and LFA-1 affinity in T cells

期刊

JOURNAL OF LEUKOCYTE BIOLOGY
卷 90, 期 1, 页码 99-109

出版社

WILEY
DOI: 10.1189/jlb.1110622

关键词

carboxypeptidase; activation; cytoplasmic tail

资金

  1. Research Agency of the Republic of Slovenia [P4-0127, J4-9425]

向作者/读者索取更多资源

T cell migration, essential for immune surveillance and response, is mediated by the integrin LFA-1. CatX, a cysteine carboxypeptidase, is involved in the regulation of T cell migration by interaction with LFA-1. We show that sequential cleavage of C-terminal amino acids from the beta(2) cytoplasmic tail of LFA-1, by CatX, enhances binding of the adaptor protein talin to LFA-1 and triggers formation of the latter's high-affinity form. As shown by SPR analysis of peptides constituting the truncated beta(2) tail, the cleavage of three C-terminal amino acids by CatX resulted in a 1.6-fold increase of talin binding. Removal of one more amino acid resulted in a 2.5-fold increase over the intact tail. CatX cleavage increased talin-binding affinity to the MD but not the MP talin-binding site on the beta(2) tail. This was shown by molecular modeling of the beta(2) tail/talin F3 complex to be a result of conformational changes affecting primarily the distal-binding site. Analysis of LFA-1 by conformation-specific mAb showed that CatX modulates LFA-1 affinity, promoting formation of high-affinity from intermediate-affinity LFA-1 but not the initial activation of LFA-1 from a bent to extended form. CatX post-translational modifications may thus represent a mechanism of LFA-1 fine-tuning that enables the trafficking of T cells. J. Leukoc. Biol. 90: 99-109; 2011.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据