title: C5a structural requirements for neutrophil receptor interaction.
abstract: 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.
authors.affiliation: Immunoscience Research Area, Abbott Laboratories, Abbott Park, IL 60064.
authors.forename: K W
authors.initials: KW
authors.lastname: Mollison
authors.forename: T A
authors.initials: TA
authors.lastname: Fey
authors.forename: R A
authors.initials: RA
authors.lastname: Krause
authors.forename: L
authors.initials: L
authors.lastname: Miller
authors.forename: R P
authors.initials: RP
authors.lastname: Edalji
authors.forename: R G
authors.initials: RG
authors.lastname: Conway
authors.forename: W
authors.initials: W
authors.lastname: Mandecki
authors.forename: M A
authors.initials: MA
authors.lastname: Shallcross
authors.forename: M
authors.initials: M
authors.lastname: Kawai
authors.forename: Y S
authors.initials: YS
authors.lastname: Or
mesh_terms: 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
chemical_list: D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D015936:Complement C5a