C5a structural requirements for neutrophil receptor interaction.
A number of C5a modifications were tested to determine effects on receptor binding to polymorphonuclear leukocyte (PMNL) membrane receptors and triggering of PMNL chemokinesis and myeloperoxidase (MPO) release. Site-directed mutagenesis was used to probe relationships of key C-terminal residues, and suggested a role for additional sites, particularly Lys19-20. A synthetic peptide based on C5a 19-30, weakly inhibited C5a binding. Potency of the C-terminal octapeptide, a full agonist, was markedly improved by a single Phe substitution for His67, and a Phe point mutation at this site was shown to enhance activity of the full recombinant protein.
Mollison
K W
KW
Immunoscience Research Area, Abbott Laboratories, Abbott Park, IL 60064.
Fey
T A
TA
Krause
R A
RA
Miller
L
L
Edalji
R P
RP
Conway
R G
RG
Mandecki
W
W
Shallcross
M A
MA
Kawai
M
M
Or
Y S
YS
D002478:Cells, Cultured; D015936:Complement C5a / Q000378:metabolism*; D006801:Humans; D009504:Neutrophils / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D015936:Complement C5a