Possible role of phosphatidylserine–hemocyanin interaction in the innate immune response of Limulus polyphemus

Phenoloxidase enzymes and the associated pro-phenoloxidase activation cascade play an essential role in the immune response of arthropods. Phenoloxidase activity can be elicited in the oxygen carrier, hemocyanin, by the addition of the artificial inducer, SDS. There is some evidence to support hemocyanin acting as a phenoloxidase in vivo; however, the identity of natural activators remains unclear. This study explores the role of the phospholipid, phosphatidylserine, as a possible natural activator of hemocyanin-derived phenoloxidase activity. Characterisation of the structural changes associated with activation of hemocyanin-derived phenoloxidase suggests that phosphatidylserine induces similar conformational changes to those caused by the artificial inducer, SDS. We propose that anionic phospholipids, in particular phosphatidylserine, may act as natural activators of hemocyanin-derived phenoloxidase.