Localization of ligand binding regions of the human formyl peptide receptor

The formyl peptide receptor is involved in the activation of human neutrophils (PMN) and their subsequent response to chemotactic peptides such as FMLP. The normal FMLP receptor has been reported to contain both high and low affinity states and to consist of several glycoprotein components, ranging in size from 40-94 kDa. However, little is known about the functional domains of the receptor. In this study we have constructed synthetic peptides corresponding to different portions of the reported receptor structure, and have tested their involvement in ligand binding. One of these peptides, corresponding to the first extracellular loop of the N-terminus end of the molecule, has been shown to specifically inhibit FMLP binding to PMN membranes. Concomitantly, this peptide exhibited the strongest direct binding to the ligand. We propose that this portion of the FMLP receptor molecule is important in receptor-ligand interactions.