Role of Plasmepsin V in Export of Diverse Protein Families from the Plasmodium falciparum Exportome
- Author(s)
- Boddey, JA; Carvalho, TG; Hodder, AN; Sargeant, TJ; Sleebs, BE; Marapana, D; Lopaticki, S; Nebl, T; Cowman, AF;
- Details
- Publication Year 2013-05,Volume 14,Issue #5,Page 532-550
- Journal Title
- TRAFFIC
- Publication Type
- Journal Article
- Abstract
- Plasmodium falciparum exports several hundred effector proteins that remodel the host erythrocyte and enable parasites to acquire nutrients, sequester in the circulation and evade immune responses. The majority of exported proteins contain the Plasmodium export element (PEXEL; RxLxE/Q/D) in their N-terminus, which is proteolytically cleaved in the parasite endoplasmic reticulum by Plasmepsin V, and is necessary for export. Several exported proteins lack a PEXEL or contain noncanonical motifs. Here, we assessed whether Plasmepsin V could process the N-termini of diverse protein families in P. falciparum. We show that Plasmepsin V cleaves N-terminal sequences from RIFIN, STEVOR and RESA multigene families, the latter of which contain a relaxed PEXEL (RxLxxE). However, Plasmepsin V does not cleave the N-terminal sequence of the major exported virulence factor erythrocyte membrane protein 1 (PfEMP1) or the PEXEL-negative exported proteins SBP-1 or REX-2. We probed the substrate specificity of Plasmepsin V and determined that lysine at the PEXEL P3 position, which is present in PfEMP1 and other putatively exported proteins, blocks Plasmepsin V activity. Furthermore, isoleucine at position P1 also blocked Plasmepsin V activity. The specificity of Plasmepsin V is therefore exquisitely confined and we have used this novel information to redefine the predicted P. falciparum PEXEL exportome.
- Publisher
- WILEY-BLACKWELL
- Keywords
- effector ; export ; malaria ; PEXEL ; Plasmepsin V ; PNEP ; trafficking
- Research Division(s)
- Chemical Biology; Infection And Immunity
- Publisher's Version
- https://doi.org/10.1111/tra.12053
- Open Access at Publisher's Site
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- © 2013 John Wiley & Sons A/S
Creation Date: 2013-05-01 12:00:00