Loops within the CD11c I domain critical for specific recognition of fibrinogen

초록

The I domains of CD11 are responsible for the binding of ligands and have a unique structure with 6-7 α helixes and 6 β sheets with interconnecting loops. To determine loops recognizing fibrinogen in CD11c I domain, five oligopeptides corresponding to CD11c loops were used to prevent fibrinogen binding to isolated CD11c I domain. The results of the inhibition experiment indicated that all of the loops except the one between E-β sheet and 6-α helix were involved in the binding to fibrinogen. The peptide βDα5 and α3α4 showed higher inhibitory activity than others, and the combination of four peptides blocked fibrinogen binding to the I domain completely. These peptides (βAα1, α3α4, βDβ5 and βFα7) could block THP-1 cell binding to fibrinogen coated surface as well. Alanine substitution of amino acids on the I domain such as Y249A and Q201A (which are on the loops βD-α5 and α3-α4 respectively) abolished fibrinogen binding, while mutation on the loop βE-α6 (Q273A) had no effect on fibrinogen binding. Taken together, the results from this study suggest that the loops on the top of CD11c I domain such as loop βA-α1, α3-α4, βD-α5 and βF-α7 are involved in fibrinogen binding, and two loops (α3-α4 and βD-α5) are more important than others for the recognition of fibrinogen. © 2002 Elsevier Science (USA).

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