Base of molecular mimicry between human ribosomal protein S19 dimer and human C5a anaphylatoxin.

The crosslinked homodimer of human ribosomal protein S19 (hRP S19) but not hRP S19 monomer shares the hC5a receptor ligation capacity with anaphylatoxin hC5a. The hRP S19 dimer engages hC5a receptor-bearing monocytes in chemotactic movement and secretion as does hC5a. Two submolecular regions essential for the receptor ligation were already identified in hRP S19 as well as in hC5a. Using the tertiary structure data base of an archaeobacterial RP S19 as template, we made a tertiary structure model of hRP S19. The obtained structure was almost entirely α-helical with two short β-sheet regions, and folds a five α-helix bundle organized around a central amphipathic α-helix. While the secondary structure components were similar to those of hC5a, the gross tertiary structure of hRP S19 was loose and the distance between the two receptor binding regions was rather big in comparison to that of hC5a. Anti-recombinant hC5a rabbit antibodies cross-recognized not only the crosslinked hRP S19 dimer but also the guinea pig (gp) RP S19 dimer, however, these antibodies reacted hRP S19 monomer and crosslinked Gln137Asn-hRP S19 mutant dimer at significantly less extents. These antibodies neutralized the monocyte attracting capacity of the hRP S19 dimer in vitro and that of the gpRP S19 dimer in vivo. We assume that the crosslinkage between Lys122 of one hRP S19 molecule and Gln137 of the other one would assemble the hC5a-like structure probably providing one of two receptor binding regions by each hRP S19 subunit.