Plasmodium falciparum dipeptidyl aminopeptidase 3 activity is important for efficient erythrocyte invasion by the malaria parasite

PLoS Pathogens
Christine LehmannEdgar Deu

Abstract

Parasite egress from infected erythrocytes and invasion of new red blood cells are essential processes for the exponential asexual replication of the malaria parasite. These two tightly coordinated events take place in less than a minute and are in part regulated and mediated by proteases. Dipeptidyl aminopeptidases (DPAPs) are papain-fold cysteine proteases that cleave dipeptides from the N-terminus of protein substrates. DPAP3 was previously suggested to play an essential role in parasite egress. However, little is known about its enzymatic activity, intracellular localization, or biological function. In this study, we recombinantly expressed DPAP3 and demonstrate that it has indeed dipeptidyl aminopeptidase activity, but contrary to previously studied DPAPs, removal of its internal prodomain is not required for activation. By combining super resolution microscopy, time-lapse fluorescence microscopy, and immunoelectron microscopy, we show that Plasmodium falciparum DPAP3 localizes to apical organelles that are closely associated with the neck of the rhoptries, and from which DPAP3 is secreted immediately before parasite egress. Using a conditional knockout approach coupled to complementation studies with wild type or mutant D...Continue Reading

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Citations

May 3, 2019·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Thomas D Lockwood
Mar 21, 2019·Frontiers in Microbiology·Manasi MishraShailja Singh
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Mar 10, 2021·Journal of Cell Science·Michele S Y Tan, Michael J Blackman

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Methods Mentioned

BETA
PCR
confocal microscopy
RAP
transfection
FACS
light
flow cytometry
size exclusion chromatography
transgenic
magnetic

Software Mentioned

image J
Axiovision
Imaris x64
Fiji
FlowJo
LAS AF
ImageJ
Adobe Photoshop CS4
Genewiz
loxPint

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