Identification of receptor-binding sites of monocyte chemotactic S19 ribosomal protein dimer

The S19 ribosomal protein (RP S19) cross-linked homo-dimer attracts monocyt e migration by binding to C5a receptor on monocytes (H Nishiura, Y Shibuya, T Yamamoto, Laboratory Investigation, 1998, 78:1615-1623). Using site-dire cted mutants of recombinant RP S19 and synthetic peptides mimicking RP S19 molecular regions, we currently identified the binding sites of the RP S19 dimer to the C5a receptor. The RP S19 dimer activated the receptor by a two -step binding mechanism as in the case of C5a. The first binding site was a basic cluster region containing a -Lys41-His42-Lys43- sequence. The second one was the -Leul31-Asp132-Arg133- moiety, localized 12 residues upstream from the COOH-terminal. The second binding triggered the chemotactic respon se. The first binding would have a role in achieving a high-binding affinit y between the ligand and receptor. The first and second ligand-binding site s of C5a receptor seem to be shared by C5a and the RP S19 dimer, although o verall homology between the amino acid sequences of these ligands is only 4 %.