Activation of the <i>Plasmodium</i> Egress Effector Subtilisin-Like Protease 1 Is Mediated by Plasmepsin X Destruction of the Prodomain
Sumit Mukherjee, Armiyaw S. Nasamu, Kelly Rubiano, Daniel E. Goldberg
Abstract
Malaria parasites replicate inside a parasitophorous vacuole within the host red blood cells. The exit of mature progeny from the infected host cells is essential for further dissemination. Parasite exit is a highly regulated, explosive process that involves membrane breakdown. To do this, the parasite utilizes a serine protease called SUB1 that proteolytically activates various effector proteins. SUB1 activity is dependent on an upstream protease called PM X, although the mechanism was unknown. Here, we describe the molecular basis for PM X-mediated SUB1 activation. PM X proteolytically degrades the inhibitory segment of SUB1, thereby activating it. The involvement of a heterologous protease is a novel mechanism for subtilisin activation.