Non-canonical maturation of two papain-family Proteases in Toxoplasma gondii

Zhicheng Dou, Isabelle Coppens, Vern B. Carruthers

Research output: Contribution to journalArticle

Abstract

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 enzymeswealso 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 knock-out parasites. Finally, we show that although maturation of TgCPL is independent of TgCPB, it may involve an additional protease(s) in conjunction with self-maturation.

Original languageEnglish (US)
Pages (from-to)3523-3534
Number of pages12
JournalJournal of Biological Chemistry
Volume288
Issue number5
DOIs
StatePublished - Feb 1 2013

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Papain
Toxoplasma
Cathepsin B
Peptide Hydrolases
Parasites
Cathepsins
Enzyme Precursors
Lysosomes
Antibodies
Enzymes
Infection

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Non-canonical maturation of two papain-family Proteases in Toxoplasma gondii. / Dou, Zhicheng; Coppens, Isabelle; Carruthers, Vern B.

In: Journal of Biological Chemistry, Vol. 288, No. 5, 01.02.2013, p. 3523-3534.

Research output: Contribution to journalArticle

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