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

Publisher: Academic Press Country of Publication: United States NLM ID: 0370713 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2449 (Electronic) Linking ISSN: 00144894 NLM ISO Abbreviation: Exp Parasitol Subsets: MEDLINE

Publication: Orlando, FL : Academic Press
Original Publication: New York.

Aminopeptidases/*metabolism ; Erythrocyte Deformability/*physiology ; Plasmodium falciparum/*enzymology; Amino Acid Sequence ; Aminopeptidases/chemistry ; Aminopeptidases/genetics ; Aminopeptidases/immunology ; Antibodies, Protozoan/immunology ; Blotting, Northern ; Blotting, Western ; Cell Adhesion/physiology ; Elasticity ; Erythrocyte Membrane/genetics ; Erythrocyte Membrane/physiology ; Erythrocytes/parasitology ; Gene Knockout Techniques ; Humans ; Microscopy, Atomic Force ; Microscopy, Electron, Transmission ; Microscopy, Fluorescence ; Plasmodium falciparum/genetics ; RNA, Protozoan/chemistry ; Real-Time Polymerase Chain Reaction ; Recombinant Proteins/chemistry ; Recombinant Proteins/genetics ; Recombinant Proteins/immunology ; Recombinant Proteins/metabolism ; Sequence Alignment ; Transfection

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.
(Copyright © 2016 Elsevier Inc. All rights reserved.)

Keywords: Cytoadherence; Erythrocyte deformability; Malaria; Plasmodium falciparum; Prolyl aminopeptidase

0 (Antibodies, Protozoan)
0 (RNA, Protozoan)
0 (Recombinant Proteins)
EC 3.4.11.- (Aminopeptidases)
EC 3.4.11.5 (prolyl aminopeptidase)

Date Created: 20160705 Date Completed: 20170215 Latest Revision: 20170215

20250114

10.1016/j.exppara.2016.06.013

27373432