Characterization of the residues of αX I-domain and ICAM-1 mediating their interactions
| Autor: | Jeongsuk Choi, Sang-Uk Nham, Jeasun Choi |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Protein Conformation
Integrin Cell Movement Cell Adhesion Leukocytes Humans Endothelium Binding site Amino Acids Molecular Biology ICAM-1 Α subunit Binding Sites biology Chemistry Cell Biology General Medicine Intercellular Adhesion Molecule-1 Leukocyte extravasation CD11c Antigen Protein Structure Tertiary HEK293 Cells Biochemistry Domain (ring theory) biology.protein Biophysics Mutagenesis Site-Directed iC3b Mutant Proteins Protein Binding |
| Zdroj: | Molecules and cells. 30(3) |
| ISSN: | 0219-1032 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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