Localization of formylpeptide binding domain using chimeric and mutagenesis approaches

The N-formylpeptide fMet-Leu-Phe (fMLP) is a small chemotactic peptide deri ved from bacterial proteins and it is a potent activator for neutrophil fun ctions. Understanding of its binding to the fMLP receptor (FPR) is inflamma tion chimeric and point mutant FPR, the following results were obtained: (i ) The amino terminal domain of the FPR is a less important region for fMLP binding, as compared to other receptors such as the C5a receptor and the IL -8 receptors;. (ii) All three extracellular loops are involved in fMLP bind ing, but the first and third loops are more important than the second loop. (iii) Several point mutations in the transmembrane domains (TMD) disrupted fMLP binding, indicating amino acid residues in the TMDs also participated in fMLP binding. These results are helpful in designing new antagonists fo r the FPR.