The complement cofactor protein (SBP1) from the barred sand bass (Paralabrax nebulifer) mediates overlapping regulatory activities of both human C4b binding protein and factor H.
We have previously shown that serum of the teleost fish barred sand bass (Paralabrax nebulifer) cleaves the alpha'-chain of human C4b and C3b. The proteins that participate in these reactions were purified, and a specific protease and a single cofactor protein were identified. Functional characterization of the recombinantly expressed sand bass cofactor protein (SBP1) and truncated forms containing short consensus repeats (SCRs) 1-2, 1-3, 1-4, 1-5, and 12-17 revealed that SBP1 and SCRs 1-4 mediate the functional activities of the human plasma regulatory protein C4bp and factor H. They form a complex with C4b, inhibit the formation, and accelerate the decay of the classical pathway C3 convertase and display cofactor activity for the cleavage of C4b. In contrast, the interaction of SBP1 and SCRs 1-4 with human C3b in all these activities was limited. This difference is due to species-specific incompatibilities between the cofactor protein and human C3b. SBP1 and SCRs 1-5 displayed full binding and cofactor activity for methylamine-treated C3 from trout, a species closely related to the sand bass. The presence of only one cofactor in the fish plasma that combines the functional activities of C4bp and factor H demonstrates that the sand bass cofactor protein is the ancestral precursor to the two complement regulatory proteins in human plasma.
Kemper
C
C
Department of Molecular Parasitology, Bernhard Nocht Institute for Tropical Medicine, Bernhard Nocht Strasse 74, D-20359 Hamburg, Germany.
Zipfel
P F
PF
Gigli
I
I
D000818:Animals; D001492:Bass / Q000502:physiology; D001798:Blood Proteins / Q000737:chemistry / Q000502:physiology*; D003001:Cloning, Molecular; D050577:Complement C3-C5 Convertases / Q000378:metabolism; D003179:Complement C3b / Q000378:metabolism; D015935:Complement C4b / Q000378:metabolism*; D017242:Complement Factor H / Q000378:metabolism*; D003165:Complement System Proteins / Q000378:metabolism; D006801:Humans; D010446:Peptide Fragments / Q000502:physiology; D010949:Plasma / Q000737:chemistry; D011485:Protein Binding / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism
D001798:Blood Proteins; C493495:CFH protein, human; D010446:Peptide Fragments; D011994:Recombinant Proteins; C105969:cofactor-related protein 1, sand bass; D003179:Complement C3b; D015935:Complement C4b; D017242:Complement Factor H; D003165:Complement System Proteins; D050577:Complement C3-C5 Convertases