C3bi receptor (complement receptor type 3) recognizes a region of complement protein C3 containing the sequence Arg-Gly-Asp.
Human phagocytes express a receptor termed complement receptor type 3 (CR3) that recognizes the complement protein fragment C3bi. We show here that CR3 recognizes a region of C3 that contains the sequence Arg-Gly-Asp (RGD). CR3 is down-modulated upon spreading of macrophages on surfaces coated with a synthetic 21-residue peptide from C3 (residues 1383-1403). This peptide was also attached to erythrocytes by coupling myristic acid to its amino terminus and allowing the myristoylated peptide to bind to erythrocytes through hydrophobic interactions. Erythrocytes coated with this RGD-containing segment of C3 were bound by macrophages, and binding could be blocked by specific monoclonal antibodies against CR3. Since CR3 recognizes a peptide sequence that contains the RGD triplet, it appears to be a member of a larger family of adhesion-promoting receptors that recognize RGD-containing proteins. However, since CR3 does not recognize a hexapeptide containing RGD, we presume that residues beyond the RGD triplet contribute to binding. We have compared the RGD-containing region of fibronectin and vitronectin, proteins known to be recognized by means of their RGD-containing regions, with those in human and murine C3. A striking homology is observed over an approximately equal to 50 amino acid sequence present in all four proteins. We suggest that this extended region of homology contains a structure recognized by adhesion-promoting receptors.
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D003176:Complement C3 / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D016177:Macrophage-1 Antigen; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000378:metabolism; D011485:Protein Binding; D011951:Receptors, Complement / Q000378:metabolism*; D013329:Structure-Activity Relationship
D003176:Complement C3; D016177:Macrophage-1 Antigen; D011951:Receptors, Complement