Plasmodium food vacuole plasmepsins are activated by falcipains

Mark E. Drew, Ritu Banerjee, Eric W. Uffman, Scott Gilbertson, Philip J. Rosenthal, Daniel E. Goldberg

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Intraerythrocytic malaria parasites use host hemoglobin as a major nutrient source. Aspartic proteases (plasmepsins) and cysteine proteases (falcipains) function in the early steps of the hemoglobin degradation pathway. There is extensive functional redundancy within and between these protease families. Plasmepsins are synthesized as integral membrane proenzymes that are activated by cleavage from the membrane. This cleavage is mediated by a maturase activity whose identity has been elusive. We have used a combination of cell biology, chemical biology, and enzymology approaches to analyze this processing event. These studies reveal that plasmepsin processing occurs primarily via the falcipains; however, if falcipain activity is blocked, autoprocessing can take place, serving as an alternate activation system. These results establish a further level of redundancy between the protease families involved in Plasmodium hemoglobin degradation.

Original languageEnglish (US)
Pages (from-to)12870-12876
Number of pages7
JournalJournal of Biological Chemistry
Volume283
Issue number19
DOIs
StatePublished - May 9 2008
Externally publishedYes

Fingerprint

Plasmodium
Vacuoles
Hemoglobins
Peptide Hydrolases
Food
Redundancy
Cytology
Membranes
Degradation
Enzyme Precursors
Cysteine Proteases
Processing
Nutrients
Malaria
Cell Biology
Parasites
Chemical activation
falcipain
plasmepsin

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Drew, M. E., Banerjee, R., Uffman, E. W., Gilbertson, S., Rosenthal, P. J., & Goldberg, D. E. (2008). Plasmodium food vacuole plasmepsins are activated by falcipains. Journal of Biological Chemistry, 283(19), 12870-12876. https://doi.org/10.1074/jbc.M708949200

Plasmodium food vacuole plasmepsins are activated by falcipains. / Drew, Mark E.; Banerjee, Ritu; Uffman, Eric W.; Gilbertson, Scott; Rosenthal, Philip J.; Goldberg, Daniel E.

In: Journal of Biological Chemistry, Vol. 283, No. 19, 09.05.2008, p. 12870-12876.

Research output: Contribution to journalArticle

Drew, ME, Banerjee, R, Uffman, EW, Gilbertson, S, Rosenthal, PJ & Goldberg, DE 2008, 'Plasmodium food vacuole plasmepsins are activated by falcipains', Journal of Biological Chemistry, vol. 283, no. 19, pp. 12870-12876. https://doi.org/10.1074/jbc.M708949200
Drew ME, Banerjee R, Uffman EW, Gilbertson S, Rosenthal PJ, Goldberg DE. Plasmodium food vacuole plasmepsins are activated by falcipains. Journal of Biological Chemistry. 2008 May 9;283(19):12870-12876. https://doi.org/10.1074/jbc.M708949200
Drew, Mark E. ; Banerjee, Ritu ; Uffman, Eric W. ; Gilbertson, Scott ; Rosenthal, Philip J. ; Goldberg, Daniel E. / Plasmodium food vacuole plasmepsins are activated by falcipains. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 19. pp. 12870-12876.
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