Poster Presentation Lorne Infection and Immunity 2019

Amino acid motifs present in effector proteins exported into the host erythrocytes of malaria parasites may be specifically recognised by the Plasmodium translocon for exported of proteins (PTEX) (#129)

Mikha Gabriela 1 2 , Benjamin Dickerman 2 , Paul Sanders 2 , Brendan Crabb 2 , Tania De Koning-Ward 1 , Paul Gilson 2
  1. Deakin University, Geelong, VIC, Australia
  2. Burnet Institute, Melbourne, VIC, Australia

Survival of the intraerythrocytic stage of Plasmodiumparasites relies heavily upon its ability to renovate its host cell by means of exporting hundreds of effector proteins. In order to reach the host erythrocyte, parasite effector proteins need to cross the parasitophorous vacuole membrane (PVM) that surrounds the intracellular parasite. The Plasmodium Translocon of Exported proteins (PTEX) provides a conduit for effector proteins to cross the PVM, however the specific mechanism by which PTEX recognises effector proteins still remains unknown. In this study, we show that one of PTEX core components, the clpB/AAA+ATPase HSP101 (Pf3D7_1116800), binds to the unique Plasmodium Export Element (PEXEL) motif that is commonly found in proteins destined for export. Specifically, single point mutations to the PEXEL motif significantly reduced binding to HSP101. To explore the intracellular location(s) of these dynamic interactions, fluorescence imaging and biochemical analysis of HSP101’s location was performed. Interestingly and despite being a part of PVM-located PTEX complex, a significant proportion of HSP101 was also found to reside inside the parasite. Furthermore, treating the parasite with secretory pathway inhibitor brefeldin-A caused trapping of HSP101 in the endoplasmic reticulum of the parasite. From these findings, we propose that HSP101 may cycle between the parasite’s endoplasmic reticulum, where it binds to newly synthesised effector proteins, and the PVM, where HSP101 then docks with the rest of PTEX and to unfold and extrude the effector proteins across the PVM into the erythrocyte.