Integrin alpha X beta 2 (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 alpha X I-domain, which is a ligand-binding moiety, is important in understanding leukocyte biology and integrin function. Previously we showed that two loops (alpha 3-alpha 4, beta D-alpha 5) around a ligand-binding face of alpha X 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 (beta F-alpha 7) for fibrinogen fragment E, the central domain of fibrinogen. The residues S-199 and Q(202) in the alpha 3-alpha 4 loop and K-243, Y-250 in the beta D-alpha 5 loop are critical for the ligand. The residues K-242, D-249, K-251, and D-252 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 alpha X I-domain. Sequence comparisons with alpha M I-domain reveal that most of the critical residues shown in alpha X I-domain are also conserved in alpha M and may have important roles in fibrinogen central domain recognition in alpha M I-domain as well. (c) 2007 Elsevier Inc. All rights reserved.