Three different conformational states of pregnancy zone protein identified by monoclonal antibodies

Human pregnancy zone protein (PZP), related to human alpha 2-macroglobulin, forms dimeric/tetrameric (360/720 kDa) species. PZP binds proteinases which cause the cleavage of internal thiol esters in the molecule. Both the binding of proteinases, i.e. chymotrypsin, (CT) to PZP, forming PZP.CT complexes, or reaction with methylamine (MA) forming PZP.MA complexes, cause transition to a new similar conformational state. Reactivity of selected monoclonal antibodies against PZP towards the three PZP derivatives demonstrated differences in the reactivity pattern. PZP and PZP.MA share one determinant, which is missing on the PZP.CT complex. PZP after transition to PZP.CT, but not to PZP.MA, presents a neodeterminant detected by one of six monoclonal antibodies. The findings demonstrate that at least three different conformational states exist for PZP and its derivatives. Access to discriminating immunochemical tools makes possible an evaluation of the relative abundance of the different complexes in vivo.