Identification of a receptor-binding region in the core segment of the human anaphylatoxin C5a.
In order to identify regions of C5a that contribute to receptor binding and functional activity of the anaphylatoxin, a series of peptides was synthesized in which core segments have been attached to C-terminal segments via native peptidic or disulfide bonds. It has been found that residues Arg40 and Arg46 in the loop-3 region of the core induce a 1000-fold increase in the affinity of the disordered C-terminal segment of C5a. The results obtained from this work lead to the conclusion that the loop-3 region is most likely the core binding site of C5a.
Vlattas
I
I
CIBA-GEIGY Corporation, Research Department, Summit, New Jersey 07901.
Sytwu
I I
II
Dellureficio
J
J
Stanton
J
J
Braunwalder
A F
AF
Galakatos
N
N
Kramer
R
R
Seligmann
B
B
Sills
M A
MA
Wasvary
J
J
D000595:Amino Acid Sequence; D001120:Arginine; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D015936:Complement C5a / Q000737:chemistry / Q000378:metabolism*; D004220:Disulfides; D006801:Humans; D007700:Kinetics; D008961:Models, Structural; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis* / Q000378:metabolism; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000378:metabolism; D017433:Protein Structure, Secondary; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000378:metabolism*
D004220:Disulfides; D010455:Peptides; D010456:Peptides, Cyclic; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D015936:Complement C5a; D001120:Arginine