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 ba ss (Paralabrax nebulifer) cleaves the alpha'-chain of human C4b and C3 b, The proteins that participate in these reactions were purified, and a specific protease and a single cofactor protein were identified. Fu nctional characterization of the recombinantly expressed sand bass cof actor protein (SBP1) and truncated forms containing short consensus re peats (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 Il, They form a complex with C4b, inhibit the formation, and accelerate the decay of the classical pathway C3 conver tase and display cofactor activity for the cleavage of C4b, In contras t, the interaction of SBP1 and SCRs 1-4 with human C3b in all these ac tivities was limited. This difference is due to species-specific incom patibilities between the cofactor protein and human C3b, SBP1 and SCRs 1-5 displayed full binding and cofactor activity for methylamine-trea ted C3 from trout, a species closely related to the sand bass. The pre sence of only one cofactor in the fish plasma that combines the functi onal activities of C4bp and factor Il demonstrates that the sand bass cofactor protein is the ancestral precursor to the two complement regu latory proteins in human plasma.