TgSUB2 is a Toxoplasma gondii rhoptry organelle processing proteinase

Steven A. Miller, Vandana Thathy, James W. Ajioka, Michael J. Blackman, Kami Kim

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

All parasites in the phylum Apicomplexa, including Toxoplasma gondii and Plasmodium falciparum, contain rhoptries, specialized secretory organelles whose contents are thought to be essential for successful invasion of host cells. Serine proteinase inhibitors have been reported to block host cell invasion by both T. gondii and P. falciparum. We describe the cloning and characterization of TgSUB2, a subtilisin-like serine proteinase, from T. gondii. Like its closest homologue P. falciparum PfSUB-2, TgSUB2 is predicted to be a type I transmembrane protein. Disruption of TgSUB2 was unsuccessful implying that TgSUB2 is an essential gene. TgSUB2 undergoes autocatalytic processing as it traffics through the secretory pathway. TgSUB2 localizes to rhoptries and associates with rhoptry protein ROP1, a potential substrate. A sequence within TgSUB2 with homology to the ROP1 cleavage site (after Glu) was identified and mutated by site-directed mutagenesis. This mutation abolished TgSUB2 auto-processing suggesting that TgSUB2 is a rhoptry protein maturase with similar specificity to the ROP1 maturase. Processing of secretory organelle contents appears to be ubiquitous among the Apicomplexa. As subtilases are present in genomes of all the Apicomplexa sequenced to date, subtilases may represent a novel chemotherapeutic target.

Original languageEnglish (US)
Pages (from-to)883-894
Number of pages12
JournalMolecular Microbiology
Volume49
Issue number4
DOIs
StatePublished - Aug 2003

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Apicomplexa
Toxoplasma
Plasmodium falciparum
Organelles
Peptide Hydrolases
Subtilisin
Proteins
Serine Proteinase Inhibitors
Secretory Pathway
Essential Genes
Serine Proteases
Site-Directed Mutagenesis
Organism Cloning
Parasites
Genome
Mutation

ASJC Scopus subject areas

  • Molecular Biology
  • Microbiology

Cite this

Miller, S. A., Thathy, V., Ajioka, J. W., Blackman, M. J., & Kim, K. (2003). TgSUB2 is a Toxoplasma gondii rhoptry organelle processing proteinase. Molecular Microbiology, 49(4), 883-894. https://doi.org/10.1046/j.1365-2958.2003.03604.x

TgSUB2 is a Toxoplasma gondii rhoptry organelle processing proteinase. / Miller, Steven A.; Thathy, Vandana; Ajioka, James W.; Blackman, Michael J.; Kim, Kami.

In: Molecular Microbiology, Vol. 49, No. 4, 08.2003, p. 883-894.

Research output: Contribution to journalArticle

Miller, SA, Thathy, V, Ajioka, JW, Blackman, MJ & Kim, K 2003, 'TgSUB2 is a Toxoplasma gondii rhoptry organelle processing proteinase', Molecular Microbiology, vol. 49, no. 4, pp. 883-894. https://doi.org/10.1046/j.1365-2958.2003.03604.x
Miller, Steven A. ; Thathy, Vandana ; Ajioka, James W. ; Blackman, Michael J. ; Kim, Kami. / TgSUB2 is a Toxoplasma gondii rhoptry organelle processing proteinase. In: Molecular Microbiology. 2003 ; Vol. 49, No. 4. pp. 883-894.
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