Identification of Critical Residues for Plasminogen Binding by the αX I-domain of the β2 integrin, αXβ2

  • Gang, Jongyun (Divisions of Science Education and Biology, Research Institute of Life Sciences, Kangwon National University) ;
  • Choi, Jeongsuk (Divisions of Science Education and Biology, Research Institute of Life Sciences, Kangwon National University) ;
  • Lee, Joo Hee (Divisions of Science Education and Biology, Research Institute of Life Sciences, Kangwon National University) ;
  • Nham, Sang-Uk (Divisions of Science Education and Biology, Research Institute of Life Sciences, Kangwon National University)
  • Received : 2007.04.05
  • Accepted : 2007.05.23
  • Published : 2007.10.31


The ${\beta}2$ integrins on leukocytes play important roles in cell adhesion, migration and phagocytosis. One of the ${\beta}2$ integrins, ${\alpha}X{\beta}2$ (CD11c/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 ${\alpha}X{\beta}2$, the ${\alpha}X$ I-domain, was found to bind plasminogen, the zymogen of plasmin, with moderate affinity ($1.92{\times}10^{-6}M$) in the presence of $Mg^{2+}$ or $Mn^{2+}$. The ${\beta}D-{\alpha}5$ loop of the ${\alpha}X$ I-domain proved to be responsible for binding, and lysine residues ($Lys^{242}$, $Lys^{243}$) 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 ${\alpha}X{\beta}2$ integrin.


Supported by : Kangwon National University


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