Anti‐idiotypic monoclonal antibody recognizes a consensus recognition site for phosphatidylserine in phosphatidylserine‐specific monoclonal antibody and protein kinase C

Abstract

In order to elucidate the molecular mechanisms responsible for the specific lipid‐protein interactions, we have undertaken structural and idiotypic analyses of a monoclonal antibody, PS4A7, which binds specifically to phosphatidylserine (PS). Here we showed that one of the anti‐idiotypic monoclonal antibodies raised against PS4A7 cross‐reacted extensively with protein kinase C (PKC) and inhibited the activation of the enzymatic activity. The binding of the anti‐idiotypic antibody to PKC was inhibited specifically by PS, but not by other phospholipids including 1,2‐diacyl‐sn‐glycero ‐3‐phospho‐d‐serine or 1,2‐diacyl‐sn‐glycero‐3‐phospho‐l‐homoserine. In contrast, the binding of the anti‐idiotypic mAb to the enzyme was significantly enhanced in the presence of either diacylglycerol or sphingosine. These findings indicate that the PS‐specific monoclonal antibody and PKC share a consensus structure which is responsible for the specific interaction with PS and both diacylglycerol and sphingosine may induce a similar conformational change which exposes the PS‐specific binding site of the enzyme.