Identification of receptor-binding sites of monocyte chemotactic S19 ribosomal protein dimer.
The S19 ribosomal protein (RP S19) cross-linked homo-dimer attracts monocyte migration by binding to C5a receptor on monocytes (H Nishiura, Y Shibuya, T Yamamoto, Laboratory Investigation, 1998, 78:1615-1623). Using site-directed 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 -Leu131-Asp132-Arg133- moiety, localized 12 residues upstream from the COOH-terminal. The second binding triggered the chemotactic response. The first binding would have a role in achieving a high-binding affinity between the ligand and receptor. The first and second ligand-binding sites of C5a receptor seem to be shared by C5a and the RP S19 dimer, although overall homology between the amino acid sequences of these ligands is only 4%.
Shibuya
Y
Y
Department of Laboratory Medicine, School of Medicine, Kumamoto University, Kumamoto, Japan.
Shiokawa
M
M
Nishiura
H
H
Nishimura
T
T
Nishino
N
N
Okabe
H
H
Takagi
K
K
Yamamoto
T
T
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive; D002465:Cell Movement / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D009154:Mutation; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
D015703:Antigens, CD; D009842:Oligopeptides; D010446:Peptide Fragments; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D012269:Ribosomal Proteins; C040343:ribosomal protein S19