Recognition of bacterial formyl peptides by FPR2 (89.21)

Abstract

Abstract Formyl peptide receptor 2 (FPR2) is a homologue to FPR1, which is known for its high-affinity binding to the E. coli-derived chemotactic peptide fMet-Leu-Phe (fMLF). Unlike FPR1, FPR2 is a low affinity receptor for fMLF, raising questions for its role in host defense. We found that FPR2 is able to respond to a variety of formylated peptides with activation of cellular functions. A pentapeptide fMet-Ile-Val-Ile-Leu from L. monocytogenes and a tetrapeptide fMet-Ile-Phe-Leu from S. aureus were ~ 100 fold more potent than fMLF in activating FPR2 suggesting that bacterial formyl peptides can be high affinity ligands for FPR2. The presence of the formyl group at the N-terminus and C-terminal interaction are both important for full activation of FPR2. In comparison, FPR1 activation through formyl peptides only requires interaction with the N-terminal formyl group. We also investigated the role of charged residues in ligand interactions of both FPR1 and FPR2 receptors. Mutation of residues 84, 85 and 284 in each receptor were not competent to effect formyl peptide activation for each receptor, however; the specificity by FPR2 agonists was directly affected in the mutational study, indicating involvement of these residues in structure conformation and downstream signaling. These data demonstrate a divergent role for FPR2 in recognizing bacterial and synthetic formyl peptides, suggesting a potential function of this receptor in host defense as well as homeostatic regulation.