Food vacuole plasmepsins are processed at a conserved site by an acidic convertase activity in Plasmodium falciparum

Ritu Banerjee, Susan E. Francis, Daniel E. Goldberg

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Intraerythrocytic Plasmodium falciparum digests vast amounts of hemoglobin within an acidic food vacuole (FV). Four homologous aspartic proteases participate in hemoglobin degradation within the FV. Plasmepsin (PM) I and II are thought to initiate degradation of the native hemoglobin molecule. PM IV and histo-aspartic protease (HAP) act on denatured globin further downstream in the pathway. PM I and II have been shown to be synthesized as zymogens and activated by proteolytic removal of a propiece. In this study, we have determined that the proteolytic processing of FV plasmepsins occurs immediately after a conserved Leu-Gly dipeptidyl motif with uniform kinetics and pH and inhibitor sensitivities. We have developed a cell-free in vitro processing assay that generates correctly processed plasmepsins. Our data suggest that proplasmepsin processing is not autocatalytic, but rather is mediated by a separate processing enzyme. This convertase requires acidic conditions and is blocked only by the calpain inhibitors, suggesting that it may be an atypical calpain-like protease.

Original languageEnglish (US)
Pages (from-to)157-165
Number of pages9
JournalMolecular and Biochemical Parasitology
Volume129
Issue number2
DOIs
StatePublished - Jul 2003

Keywords

  • Calpain
  • Convertase
  • Plasmepsin
  • Protease

ASJC Scopus subject areas

  • Parasitology
  • Molecular Biology

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