Identification of critical residues for plasminogen binding by the alphaX I-domain of the beta2 integrin, alphaXbeta2

The beta2 integrins on leukocytes play important roles in cell adhesion, migration and phagocytosis. One of the beta2 integrins, alphaXbeta2 (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 a...

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Bibliographic Details
Published in:	Molecules and cells Vol. 24; no. 2; p. 240
Main Authors:	Gang, Jongyun, Choi, Jeongsuk, Lee, Joo Hee, Nham, Sang-Uk
Format:	Journal Article
Language:	English
Published:	United States 31-10-2007
Subjects:	Amino Acids - chemistry Amino Acids - metabolism Binding Sites Crystallography, X-Ray Humans Integrin alphaXbeta2 - chemistry Integrin alphaXbeta2 - metabolism Kinetics Lysine - analogs & derivatives Mutant Proteins - metabolism Peptides - metabolism Plasminogen - metabolism Protein Binding Protein Structure, Tertiary Recombinant Fusion Proteins - metabolism Structure-Activity Relationship Surface Plasmon Resonance
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Summary:	The beta2 integrins on leukocytes play important roles in cell adhesion, migration and phagocytosis. One of the beta2 integrins, alphaXbeta2 (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 alphaXbeta2, the alphaX I-domain, was found to bind plasminogen, the zymogen of plasmin, with moderate affinity (1.92 X 10-(6) M) in the presence of Mg(2+) or Mn(2+). The betaD-alpha5 loop of the alphaX 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 alphaX 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 alphaXbeta2 integrin.
ISSN:	1016-8478