title: Phylogeny of C4b-C3b cleaving activity: similar fragmentation patterns of human C4b and C3b produced by lower animals.
abstract: Functional and structural studies of the activated proteins of the complement system C4b and C3b have led to the identification of cleavage products resulting from the effect of the regulatory proteins, factor I, H, and C4b binding protein (bp). In this paper we report the results of studies that investigated the capacity of plasma or serum from a wide range of phylogenetic species to yield similar cleavage products. Sera and plasma from mammals, reptiles, amphibia, and fishes are capable of cleaving fluid phase human C4b and C3b, generating apparently the same fragments as observed using normal human serum: alpha 2, alpha 3, alpha 4 from the alpha' chain of C4b: and alpha-68, alpha-46, alpha-43, and alpha-30 from the alpha' chain of C3b. When C3b bound to a cell membrane is used C3c and C3dg are generated. The generation of these fragments from C3bi is a dose-dependent reaction. There is no correlation between the evolution of the species and the quantitative capability to degrade the substrates. Birds possess only a limited capability to degrade the alpha' chain of C4b and have no cleaving activity for C3b, whereas sera from more primitive vertebrate species (chondrichthyes and agnatha) fail to participate in the reaction. Contrary to other species, the proteins in fish serum or plasma responsible for the degradation of C4b and C3b show a unique requirement for Ca2+ ions. Magnesium and barium are less effective, and in their presence a 65,000 dalton intermediate product is observed. These results demonstrate that protein(s) displaying proteolytic activity for products of complement activation, probably related to I, H, and C4bp, are present in plasma of species whose evolution have preceded humans by 300 million years. Moreover, the recognition of human substrates and the generation of fragments identical to those produced by human serum suggests that human C4b and C3b share structural characteristics with their evolutionary ancestors in the serum or plasma of the species studied.
authors.forename: T
authors.initials: T
authors.lastname: Kaidoh
authors.forename: I
authors.initials: I
authors.lastname: Gigli
mesh_terms: D000818:Animals; D005075:Biological Evolution; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology; D003179:Complement C3b / Q000378:metabolism*; D003181:Complement C4 / Q000378:metabolism*; D015935:Complement C4b; D006801:Humans; D008970:Molecular Weight; D010446:Peptide Fragments / Q000032:analysis; D010447:Peptide Hydrolases / Q000097:blood; D012995:Solubility; D013045:Species Specificity; D013379:Substrate Specificity
chemical_list: D003181:Complement C4; D010446:Peptide Fragments; D003179:Complement C3b; D015935:Complement C4b; D010447:Peptide Hydrolases; D002118:Calcium