Identification of critical residues for plasminogen binding by the αX I-domain of the β2 integrin, αXβ2

초록

The beta 2 integrins on leukocytes play important roles in cell adhesion, migration and phagocytosis. One of the beta 2 integrins, alpha X beta 2 (CDllc/CD18), is known to bind ligands such as fibrinogen, Thy-1 and iC3b, but its function is not well characterized. To understand its biological roles, we attempted to identify novel ligands. The functional moiety of alpha XP2, the alpha X I-domain, was found to bind plasminogen, the zymogen of plasmin, with moderate affinity (1.92 x 10(-6) M) in the presence of Mg2+ or Mn2+. The beta D-alpha 5 loop of the alpha X I-domain proved to be responsible for binding, and lysine residues (LYS242, LYS243) in the loop were the most important for recognizing plasminogen. An excess amount of the lysine analog, 6-aminohexanoic acid, inhibited alpha X I-domain binding to plasminogen, indicating that binding is lysine-dependent. The results of this study indicate that leukocytes regulate plasminogen activation, and consequently plasmin activities, through an interaction with aXP2 integrin.

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