Circulating human pregnancy-associated plasma protein-A is disulfide-bridged to the proform of eosinophil major basic protein

A previously unrecognized association between pregnancy-associated plasma protein-A (PAPP-A) and the proform of eosinophil major basic protein (proMBP) is demonstrated. PAPP-A isolated from pooled pregnancy serum is shown to be a disulfide-bridged complex with proMBP (PAPP-A/proMBP) in which the subunits of the constituents are present in a 1:1 molar ratio. The results are the outcome of analysis of tryptic and CNBr/tryptic peptides from PAPP-A/proMBP, sequence analysis of intact and reduced and carboxymethylated PAPP-A/proMBP, and reaction with monoclonal antibodies directed against MBP and its proform. In addition, it is shown that commercial polyclonal anti-PAPP-A is polyspecific, also reacting with MBP.