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A Plasmodium falciparum S33 proline aminopeptidase is associated with changes in erythrocyte deformability

Title: A Plasmodium falciparum S33 proline aminopeptidase is associated with changes in erythrocyte deformability
Authors: da Silva, FL; Dixon, MWA; Stack, CM; Teuscher, F; Taran, E; Jones, MK; Lovas, E; Tilley, L; Brown, CL; Trenholme, KR; Dalton, JP; Gardiner, DL; Skinner-Adams, TS
Publication Year: 2016
Collection: University of Technology Sydney: OPUS - Open Publications of UTS Scholars
Subject Terms: Mycology & Parasitology; Erythrocytes; Erythrocyte Membrane; Humans; Plasmodium falciparum; Aminopeptidases; Recombinant Proteins; RNA; Protozoan; Antibodies; Microscopy; Electron; Transmission; Fluorescence; Atomic Force; Blotting; Western; Northern; Transfection; Sequence Alignment; Cell Adhesion; Amino Acid Sequence; Erythrocyte Deformability; Elasticity; Gene Knockout Techniques; Real-Time Polymerase Chain Reaction
Description: © 2016 Elsevier Inc. Infection with the apicomplexan parasite Plasmodium falciparum is a major cause of morbidity and mortality worldwide. One of the striking features of this parasite is its ability to remodel and decrease the deformability of host red blood cells, a process that contributes to disease. To further understand the virulence of Pf we investigated the biochemistry and function of a putative Pf S33 proline aminopeptidase (PfPAP). Unlike other P. falciparum aminopeptidases, PfPAP contains a predicted protein export element that is non-syntenic with other human infecting Plasmodium species. Characterization of PfPAP demonstrated that it is exported into the host red blood cell and that it is a prolyl aminopeptidase with a preference for N-terminal proline substrates. In addition genetic deletion of this exopeptidase was shown to lead to an increase in the deformability of parasite-infected red cells and in reduced adherence to the endothelial cell receptor CD36 under flow conditions. Our studies suggest that PfPAP plays a role in the rigidification and adhesion of infected red blood cells to endothelial surface receptors, a role that may make this protein a novel target for anti-disease interventions strategies.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: unknown
ISSN: 0014-4894
Relation: Experimental Parasitology; Experimental Parasitology, 2016, 169 pp. 13 - 21; http://hdl.handle.net/10453/103626
Availability: http://hdl.handle.net/10453/103626
Accession Number: edsbas.4DB40741
Database: BASE