Switch moiety in agonist/antagonist dual effect of S19 ribosomal protein dimer on leukocyte chemotactic C5a receptor.
The cross-linked homodimer of S19 ribosomal protein (RP S19) induces monocyte predominant infiltration due to a dual effect on the C5a receptor in leukocyte chemotaxis, agonistic to monocytes and antagonistic to polymorphonuclear leukocytes (PMN) (H. Nishiura, Y. Shibuya, T. Yamamoto, Lab Invest 1998, 78:1615-1623). The agonistic ligand moiety was recently determined to be -Leu131-Asp132-Arg133- (Y. Shibuya et al, Am J Pathol 2001, 159:2293-2301). In this study we determined the moiety responsible for the antagonistic function. A C-terminal analogue peptide of RP S19, with 18 residues containing the agonistic ligand moiety as a part, reproduced the dual function in the leukocyte chemotaxis. A C5a analogue peptide attracted PMN as well as monocytes. When C-terminal 12 residues of RP S19 after the agonistic moiety, IAGQVAAANKKH, were connected to the C5a peptide, the chimeric peptide newly obtained the dual function, indicating that the C-terminal portion of RP S19 functions as a converter from the agonist to the antagonist. C-terminal truncation analyses indicated that the C-terminal His was not essential but the next Lys was necessary for the converter function. The homodimer of a mutant RP S19 that was truncated for the C-terminal 4 residues lost the monocyte selectivity in the leukocyte infiltration in vivo as in the case of the leukocyte chemotaxis in vitro. These results indicated that the conversion of the RP S19 dimer from agonist to antagonist of C5a receptor is attributed to the IAGQVAAANKK moiety between Ile134 and Lys144.
Shrestha
Arjun
A
Division of Molecular Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Shiokawa
Megumi
M
Nishimura
Takumasa
T
Nishiura
Hiroshi
H
Tanaka
Yuji
Y
Nishino
Norikazu
N
Shibuya
Yoko
Y
Yamamoto
Tetsuro
T
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D015936:Complement C5a / Q000502:physiology*; D017931:DNA Primers; D019281:Dimerization; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000502:physiology*; D011994:Recombinant Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D012269:Ribosomal Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*
D015703:Antigens, CD; D017931:DNA Primers; D009842:Oligopeptides; D010446:Peptide Fragments; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D011994:Recombinant Proteins; D012269:Ribosomal Proteins; C040343:ribosomal protein S19; D015936:Complement C5a