J Biol Chem. 2012 Dec 18. [Epub ahead of print]
Non-canonical maturation of two papain-family proteases in Toxoplasma gondii
Dou Z, Coppens I, Carruthers VB.
University of Michigan, United States
Proteases regulate key events during infection by the pervasive intracellular parasite Toxoplasma gondii. Understanding how parasite proteases mature from an inactive zymogen to an active enzyme is expected to inform new strategies for blocking their actions. Herein, we show that T. gondii cathepsin B protease (TgCPB) does not undergo self-maturation, but instead requires the expression of a second papain-family cathepsin protease, TgCPL. Using recombinant enzymes we also show that TgCPL is capable of partially maturing TgCPB in vitro. Consistent with this interrelationship, antibodies with validated specificity detected TgCPB in the lysosome-like vacuolar compartment along with TgCPL. Our findings also establish that TgCPB does not localize to the rhoptries as previously reported. Accordingly, rhoptry morphology and rhoptry protein maturation are normal in TgCPB knockout parasites. Finally, we show that while maturation of TgCPL is independent of TgCPB, it may involve an additional protease(s) in conjunction with self-maturation.
PMID: 23250753 [PubMed - as supplied by publisher]