Characterization of the Residues of αX I-Domain and ICAM-1 Mediating Their Interactions

초록

Integrin alpha X beta 2 performs a significant role in leukocyte functions including phagocytosis and migration, and binds to a variety of ligands, including fibrinogen, iC3b, and ICAM-1. A particular domain of the alpha subunit of the integrin - the alpha X I-domain - is a ligand binding site, and the interaction of the alpha X I-domain and ICAM-1 on the endothelium is an important step in leukocyte extravasation. In order to elucidate the structural aspects of this interaction, we defined the moieties of the alpha X and ICAM-1 relevant to their interaction in this study. It was determined that the ICAM-1 binding sites of the alpha X I-domain were located in the alpha 3 alpha 4, beta D alpha 5, and beta F alpha 7 loops at the top surface of the I-domain. The residues Q(202), K-242, K-243, E-298 and D-299 on these loops were crucial for the recognition of ICAM-1. Among these residues, K-242 and K-243 on the beta D alpha 5 loop were found to be the most salient, thereby suggesting an ionic interaction between these proteins. Domain 3 of ICAM-1 was identified as a primary binding site for the alpha X I-domain. Two regions of domain 3 (D(229)QRLNPTV and E(254)DEGTQRL) perform critical functions in the binding of the alpha X I-domain. Especially, the residue E(254)DEG, is most important with regard to the alpha X I-domain.

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