The orphan receptor C5L2 has high affinity binding sites for complement fragments C5a and C5a des-Arg(74).
The substantial variations in the responses of cells to the anaphylatoxin C5a and its desarginated form, C5adR(74), suggest that more than one type of cell surface receptor for these ligands might exist. However, only a single receptor for C5a and C5adR(74), CD88, has been characterized to date. Here we report that the orphan receptor C5L2/gpr77, which shares 35% amino acid identity with CD88, binds C5a with high affinity but has a 10-fold higher affinity for C5adR(74) than CD88. C5L2 also has a moderate affinity for anaphylatoxin C3a, but cross-competition studies suggest that C3a binds to a distinct site from C5a. C4a was able to displace C3a, suggesting that C5L2, like the C3a receptor, may have a low binding affinity for this anaphylatoxin. Unlike CD88 and C3a receptor, C5L2 transfected into RBL-2H3 cells does not support degranulation or increases in intracellular [Ca(2+)] and is not rapidly internalized in response to ligand binding. However, ligation of C5L2 by anaphylatoxin did potentiate the degranulation response to cross-linkage of the high affinity IgE receptor by a pertussis toxin-sensitive mechanism. These results suggest that C5L2 is an anaphylatoxin-binding protein with unique ligand binding and signaling properties.
Cain
Stuart A
SA
Department of Neurology, University of Sheffield Medical School, Beech Hill Road, Sheffield, S10 2RX, United Kingdom.
Monk
Peter N
PN
D000595:Amino Acid Sequence; D000706:Anaphylatoxins; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry; D001665:Binding Sites; D001667:Binding, Competitive; D003001:Cloning, Molecular; D015936:Complement C5a / Q000737:chemistry*; D015937:Complement C5a, des-Arginine / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D011485:Protein Binding; D051381:Rats; D044087:Receptor, Anaphylatoxin C5a; D019707:Receptors, Chemokine / Q000737:chemistry* / Q000378:metabolism*; D011951:Receptors, Complement / Q000737:chemistry; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D000706:Anaphylatoxins; D015703:Antigens, CD; C417003:C5aR2 protein, human; D015937:Complement C5a, des-Arginine; D008024:Ligands; D008565:Membrane Proteins; D044087:Receptor, Anaphylatoxin C5a; D019707:Receptors, Chemokine; D011951:Receptors, Complement; D011994:Recombinant Proteins; C085567:complement C3a receptor; D015936:Complement C5a