Structure-function relationships of human C5a and C5aR.
Using peptides that represent linear regions of the powerful complement activation product, C5a, or loops that connect the four alpha helices of C5a, we have defined the ability of these peptides to reduce binding of (125)I-C5a to human neutrophils, inhibit chemotactic responses of neutrophils to C5a, and reduce H(2)O(2) production in neutrophils stimulated with PMA. The data have defined likely sites of interaction of C5a with C5aR. The peptides had no functional activity per se on neutrophils and did not interfere with neutrophil responses to the unrelated chemotactic peptide, N-formyl-Met-Leu-Phe. Although previous data have suggested that there are two separate sites on C5a reactive with C5aR, the current data suggest that C5a interacts with C5aR in a manner that engages three discontinuous regions of C5a.
Huber-Lang
Markus S
MS
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Sarma
J Vidya
JV
McGuire
Stephanie R
SR
Lu
Kristina T
KT
Padgaonkar
Vaishalee A
VA
Younkin
Ellen M
EM
Guo
Ren Feng
RF
Weber
Christian H
CH
Zuiderweg
Erik R
ER
Zetoune
Firas S
FS
Ward
Peter A
PA
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D001667:Binding, Competitive / Q000276:immunology; D002464:Cell Migration Inhibition; D002634:Chemotaxis, Leukocyte; D015936:Complement C5a / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D007457:Iodine Radioisotopes / Q000378:metabolism; D008969:Molecular Sequence Data; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000138:chemical synthesis / Q000378:metabolism / Q000502:physiology; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology
D015703:Antigens, CD; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D006861:Hydrogen Peroxide; D013755:Tetradecanoylphorbol Acetate