title: A Plasmodium falciparum S33 proline aminopeptidase is associated with changes in erythrocyte deformability.
abstract: 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.
authors.affiliation: Institute of Parasitology, McGill University, Canada; QIMR Berghofer Medical Research Institute, Australia.
authors.forename: Fabio L
authors.initials: FL
authors.lastname: da Silva
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Institute, University of Melbourne, Australia; ARC Centre of Excellence for Coherent X-Ray Science, Melbourne, Australia.
authors.forename: Matthew W A
authors.initials: MW
authors.lastname: Dixon
authors.affiliation: School of Science and Health, University of Western Sydney, Australia.
authors.forename: Colin M
authors.initials: CM
authors.lastname: Stack
authors.affiliation: QIMR Berghofer Medical Research Institute, Australia.
authors.forename: Franka
authors.initials: F
authors.lastname: Teuscher
authors.affiliation: Australian Institute for Bioengineering & Nanotechnology, University of Queensland, Australia; The Australian National Fabrication Facility, Queensland Node, Brisbane, Australia.
authors.forename: Elena
authors.initials: E
authors.lastname: Taran
authors.affiliation: School of Veterinary Sciences, University of Queensland, Australia.
authors.forename: Malcolm K
authors.initials: MK
authors.lastname: Jones
authors.affiliation: School of Veterinary Sciences, University of Queensland, Australia.
authors.forename: Erica
authors.initials: E
authors.lastname: Lovas
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Institute, University of Melbourne, Australia; ARC Centre of Excellence for Coherent X-Ray Science, Melbourne, Australia.
authors.forename: Leann
authors.initials: L
authors.lastname: Tilley
authors.affiliation: School of Natural Sciences, Griffith University, Brisbane, Queensland 4111, Australia; Eskitis Institute for Drug Discovery, Griffith University, Queensland, Australia.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Brown
authors.affiliation: QIMR Berghofer Medical Research Institute, Australia; School of Medicine, University of Queensland, Australia.
authors.forename: Katharine R
authors.initials: KR
authors.lastname: Trenholme
authors.affiliation: Institute of Parasitology, McGill University, Canada; School of Biological Sciences, Queen's University Belfast, Northern Ireland, United Kingdom.
authors.forename: John P
authors.initials: JP
authors.lastname: Dalton
authors.affiliation: QIMR Berghofer Medical Research Institute, Australia; Eskitis Institute for Drug Discovery, Griffith University, Queensland, Australia.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Gardiner
authors.affiliation: School of Natural Sciences, Griffith University, Brisbane, Queensland 4111, Australia; Eskitis Institute for Drug Discovery, Griffith University, Queensland, Australia. Electronic address: t.skinner-adams@griffith.edu.au.
authors.forename: Tina S
authors.initials: TS
authors.lastname: Skinner-Adams
mesh_terms: D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000913:Antibodies, Protozoan / Q000276:immunology; D015152:Blotting, Northern; D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology; D004548:Elasticity; D004907:Erythrocyte Deformability / Q000502:physiology*; D004910:Erythrocyte Membrane / Q000235:genetics / Q000502:physiology; D004912:Erythrocytes / Q000469:parasitology; D055786:Gene Knockout Techniques; D006801:Humans; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000235:genetics; D016053:RNA, Protozoan / Q000737:chemistry; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016415:Sequence Alignment; D014162:Transfection
chemical_list: D000913:Antibodies, Protozoan; D016053:RNA, Protozoan; D011994:Recombinant Proteins; D000626:Aminopeptidases; C022450:prolyl aminopeptidase
keywords: Cytoadherence; Erythrocyte deformability; Malaria; Plasmodium falciparum; Prolyl aminopeptidase