Regulated Unmasking of the Cryptic Binding Site for Integrin αMβ2 in the γC-Domain of Fibrinogen

• DOI: 10.1021/bi026324c
• Publication Date: 2002-10-22T04:43:10Z
• Authors: Valeryi K. Lishko; Bohdan Kudryk; Valentin P. Yakub...; Vivien C. Yee; Tatiana P. Ugarova
• Keywords: Proteolysis

Fibrinogen is a ligand for leukocyte integrin αMβ2 (CD11b/CD18, Mac-1) and mediates adhesion migration of leukocytes during the immune-inflammatory responses. The binding site resides in γC, constituent subdomain D-domain fibrinogen. sequence γ383−395 (P2-C) γC was implicated as major αMβ2. It unknown why on can bind to immobilized fibrinogen presence high concentrations soluble plasma. In this study, we have investigated accessibility We found that αMβ2-binding cryptic identified mechanism regulates its unmasking. Proteolytic removal small COOH-terminal segment(s) γ397/405−411, converted D100 fragment fibrinogen, which contains intact not able inhibit αMβ2-expressing cells, into D98, effectively inhibited cell adhesion. but D100, bound recombinant αMI-domain, αMI-domain recognition peptide, αM(Glu253−Arg261). Exposure P2-C D98 probed with site-specific mAb. accessible becomes exposed D98. also unmasked by immobilization onto plastic deposition extracellular matrix. Thus, exposure proteolysis correlates unmasking D-domain. These results demonstrate conformational alterations regulate suggest processes relevant tissue injury inflammation are likely be involved activation