Critical residues of alphaX I-domain recognizing fibrinogen central domain

• Published in: Biochemical and biophysical research communications Vol. 355; no. 4; pp. 1058 - 1063
• Main Authors: Lee, Joo Hee, Choi, Jeongsuk, Nham, Sang-Uk
• Format: Journal Article
• Language: English
• Published: United States 20-04-2007
• Subjects: Amino Acid Motifs; Crystallography, X-Ray; Fibrinogen - chemistry; Fibrinogen - metabolism; Humans; Kinetics; Models, Molecular; Molecular Sequence Data; Mutation - genetics; Protein Binding; Protein Structure, Tertiary; Sequence Alignment
• ISSN: 0006-291X

Integrin alphaXbeta2 (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 alphaX I-domain, which is a ligand-binding moiety, is important in understanding leukocyte biology and integrin function. Previously we showed that two loops (alpha3-alpha4, betaD-alpha5) around a ligand-binding face of alphaX 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 (betaF-alpha7) for fibrinogen fragment E, the central domain of fibrinogen. The residues S(199) and Q(202) in the alpha3-alpha4 loop and K(243), Y(250) in the betaD-alpha5 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 alphaX I-domain. Sequence comparisons with alphaM I-domain reveal that most of the critical residues shown in alphaX I-domain are also conserved in alphaM and may have important roles in fibrinogen central domain recognition in alphaM I-domain as well.