Characterization of the residues of αX I-domain and ICAM-1 mediating their interactions.
Integrin αXβ2 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 α subunit of the integrin - the αX I-domain - is a ligand binding site, and the interaction of the αX 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 αX and ICAM-1 relevant to their interaction in this study. It was determined that the ICAM-1 binding sites of the αX I-domain were located in the α3α4, βDα5, and βFα7 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 βDα5 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 αX I-domain. Two regions of domain 3 (D(229)QRLNPTV and E(254)DEGTQRL) perform critical functions in the binding of the αX I-domain. Especially, the residue E(254)DEG, is most important with regard to the αX I-domain.
Choi
Jeongsuk
J
Divisions of Science Education and Biology, Kangwon National University, Chuncheon, 200-701, Korea.
Choi
Jeasun
J
Nham
Sang-Uk
SU
D000596:Amino Acids / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D039521:CD11c Antigen / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D004727:Endothelium / Q000378:metabolism* / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary / Q000235:genetics
D000596:Amino Acids; D039521:CD11c Antigen; D050505:Mutant Proteins; D018799:Intercellular Adhesion Molecule-1