Critical residues of αX I-domain recognizing fibrinogen central domain

Integrin αXβ2 (CD11c/CD18), which binds several ligands such as fibrinogen and iC3b, has important roles in leukocyte functions including phagocytosis and migration. Establishment of structure and functional relationship in αX I-domain, which is a ligand-binding moiety, is important in understanding leukocyte biology and integrin function. Previously we showed that two loops (α3–α4, βD–α5) around a ligand-binding face of αX I-domain are important for the binding of the fibrinogen molecule. In this study, we took the further step of identifying critical residues in these loops and in a supportive loop (βF–α7) for fibrinogen fragment E, the central domain of fibrinogen. The residues S199 and Q202 in the α3–α4 loop and K243, Y250 in the βD–α5 loop are critical for the ligand. The residues K242, D249, K251, and D252 are important but less critical for fibrinogen fragment E. The involvement of the residues in the 3-dimensional model of the I-domain suggests that several amino acid sequences in fibrinogen fragment E are responsible for αX I-domain. Sequence comparisons with αM I-domain reveal that most of the critical residues shown in αX I-domain are also conserved in αM and may have important roles in fibrinogen central domain recognition in αM I-domain as well.