Article: article from journal or magazin.
Cathepsin X cleavage of the beta2 integrin regulates talin-binding and LFA-1 affinity in T cells.
Journal of Leukocyte Biology
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 β(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 β(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 β(2) tail. This was shown by molecular modeling of the β(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.
Antigens, CD18/chemistry, Antigens, CD18/metabolism, Blotting, Western, Cathepsins/chemistry, Cathepsins/metabolism, Cell Separation, Chemotaxis, Leukocyte/physiology, Electrophoresis, Polyacrylamide Gel, Flow Cytometry, Humans, Immunoprecipitation, Jurkat Cells, Lymphocyte Function-Associated Antigen-1/chemistry, Lymphocyte Function-Associated Antigen-1/metabolism, Microscopy, Fluorescence, Models, Molecular, Polymerase Chain Reaction, Protein Binding, Protein Processing, Post-Translational/immunology, T-Lymphocytes/immunology, T-Lymphocytes/metabolism, Talin/chemistry, Talin/metabolism, Transfection
Web of science
Last modification date