Characterization of plasmepsin V, a membrane-bound aspartic protease homolog in the endoplasmic reticulum of Plasmodium falciparum

Michael Klemba, Daniel E. Goldberg

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

Aspartic proteases participate in a wide variety of cellular processes in eukaryotic organisms. The genome of the human malaria parasite Plasmodium falciparum encodes 10 aspartic protease homologs. Functions have been assigned to four of these: plasmepsins I, II, IV and histo-aspartic protease are key players in the catabolism of hemoglobin in the food vacuole. The functions of the other six remain obscure. To better understand the roles of aspartic proteases in blood stage growth and asexual reproduction of P. falciparum, we have characterized the biosynthesis, cellular location and pepstatin-binding properties of plasmepsin V (PM V). PM V is expressed over the course of asexual intraerythrocytic development. The amount of PM V in the parasite is lowest in the ring stage and increases steadily through schizogony. The proregion of this aspartic protease homolog exhibits remarkable interspecies diversity and appears not to be removed following biosynthesis. In intraerythrocytic parasites, PM V is located in the endoplasmic reticulum but not in ERD2-associated Golgi structures. Fractionation and solubilization experiments demonstrate that PM V is an integral membrane protein, a result that is consistent with the presence of a C-terminal putative transmembrane domain in the PM V sequence. In contrast to the food vacuole plasmepsins, detergent-solubilized PM V does not bind the aspartic protease inhibitor pepstatin. Together, these results strongly suggest that the role of PM V in P. falciparum is distinct from those of previously characterized plasmepsins.

Original languageEnglish
Pages (from-to)183-191
Number of pages9
JournalMolecular and Biochemical Parasitology
Volume143
Issue number2
DOIs
StatePublished - Oct 2005

Keywords

  • Aspartic protease
  • Endoplasmic reticulum
  • Pepstatin
  • Plasmepsin
  • Plasmodium falciparum

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