Sequence γ377-395(P2), but not γ190-202(P1), is the binding site for the αMI-domain of integrin αMβ2 in the αC-domain of fibrinogen

Tatiana P. Ugarova, Valeryi K. Lishko, Nataly P. Podolnikova, Nobuo Okumura, Sergei M. Merkulov, Valentin P. Yakubenko, Vivien C. Yee, Susan T. Lord, Thomas A. Haas

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


The interaction between the leukocyte integrin αMβ2 (CD11b/CD18, Mac-1, CR3) and fibrinogen mediates the recruitment of phagocytes during the inflammatory response. Previous studies demonstrated that peptides P2 and P1, duplicating γ377-395 and γ190-202 sequences in the γC domain of fibrinogen, respectively, blocked the fibrinogen-binding function of αMβ2, implicating these sequences as possible binding sites for αMβ2. To determine the role of these sequences in integrin binding, recombinant wild-type and mutant γC domains were prepared, and their interactions with the αMI-domain, a ligand recognition domain within αMβ2, were tested. Deletion of γ383-411 (P2-C) and γ377-411 produced γC mutants which were defective in binding to the αMI-domain. In contrast, alanine mutations of several residues in P1 did not affect αMI-domain binding, and simultaneous mutations in P1 and deletion of P2 did not decrease the binding function of γC further. Verifying the significance of P2, inserting P2-C and the entire P2 into the homologous position of the βC-domain of fibrinogen imparted the higher αMI-domain binding ability to the chimeric proteins. To further define the molecular requirements for the P2-C activity, synthetic peptides derived from P2-C and a peptide array covering P2-C have been analyzed, and a minimal recognition motif was localized to γ390NRLTIG395. Confirming a critical role of this sequence, the cyclic peptide NRLTIG retained full activity inherent to P2-C, with Arg and Leu being important residues. Thus, these data demonstrate the essential role of the P2, but not P1, sequence for binding of γC by the αMI-domain and suggest that the adhesive function of P2 depends on the minimal recognition motif NRLTIG.

Original languageEnglish (US)
Pages (from-to)9365-9373
Number of pages9
Issue number31
StatePublished - Aug 12 2003
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry


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