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 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Plasmodium falciparum
Vacuoles
Food
Hemoglobins
Peptide Hydrolases
glycylleucine
Enzyme Precursors
Food Handling
Calpain
Globins
plasmepsin
Enzymes
plasmepsin II

Keywords

  • Calpain
  • Convertase
  • Plasmepsin
  • Protease

ASJC Scopus subject areas

  • Molecular Biology
  • Parasitology

Cite this

Food vacuole plasmepsins are processed at a conserved site by an acidic convertase activity in Plasmodium falciparum. / Banerjee, Ritu; Francis, Susan E.; Goldberg, Daniel E.

In: Molecular and Biochemical Parasitology, Vol. 129, No. 2, 07.2003, p. 157-165.

Research output: Contribution to journalArticle

Banerjee, Ritu ; Francis, Susan E. ; Goldberg, Daniel E. / Food vacuole plasmepsins are processed at a conserved site by an acidic convertase activity in Plasmodium falciparum. In: Molecular and Biochemical Parasitology. 2003 ; Vol. 129, No. 2. pp. 157-165.
@article{a87354760490458ebbff6ca83ef6cb13,
title = "Food vacuole plasmepsins are processed at a conserved site by an acidic convertase activity in Plasmodium falciparum",
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.",
keywords = "Calpain, Convertase, Plasmepsin, Protease",
author = "Ritu Banerjee and Francis, {Susan E.} and Goldberg, {Daniel E.}",
year = "2003",
month = "7",
doi = "10.1016/S0166-6851(03)00119-1",
language = "English (US)",
volume = "129",
pages = "157--165",
journal = "Molecular and Biochemical Parasitology",
issn = "0166-6851",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Food vacuole plasmepsins are processed at a conserved site by an acidic convertase activity in Plasmodium falciparum

AU - Banerjee, Ritu

AU - Francis, Susan E.

AU - Goldberg, Daniel E.

PY - 2003/7

Y1 - 2003/7

N2 - 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.

AB - 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.

KW - Calpain

KW - Convertase

KW - Plasmepsin

KW - Protease

UR - http://www.scopus.com/inward/record.url?scp=0038691865&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038691865&partnerID=8YFLogxK

U2 - 10.1016/S0166-6851(03)00119-1

DO - 10.1016/S0166-6851(03)00119-1

M3 - Article

VL - 129

SP - 157

EP - 165

JO - Molecular and Biochemical Parasitology

JF - Molecular and Biochemical Parasitology

SN - 0166-6851

IS - 2

ER -