Details

Autor(en) / Beteiligte

• Chisholm, Scott A.
• Kalanon, Ming
• Nebl, Thomas
• Sanders, Paul R.
• Matthews, Kathryn M.
• Dickerman, Benjamin K.
• Gilson, Paul R.
• Koning‐Ward, Tania F.

Titel

The malaria PTEX component PTEX88 interacts most closely with HSP101 at the host–parasite interface

Ist Teil von

• The FEBS journal, 2018-06, Vol.285 (11), p.2037-2055

Ort / Verlag

England: Blackwell Publishing Ltd

Erscheinungsjahr

2018

Quelle

Wiley Online Library All Journals

Beschreibungen/Notizen

• The pathogenic nature of malaria infections is due in part to the export of hundreds of effector proteins that actively remodel the host erythrocyte. The Plasmodium translocon of exported proteins (PTEX) has been shown to facilitate the trafficking of proteins into the host cell, a process that is essential for the survival of the parasite. The role of the auxiliary PTEX component PTEX88 remains unclear, as previous attempts to elucidate its function through reverse genetic approaches showed that in contrast to the core components PTEX150 and HSP101, knockdown of PTEX88 did not give rise to an export phenotype. Here, we have used biochemical approaches to understand how PTEX88 assembles within the translocation machinery. Proteomic analysis of the PTEX88 interactome showed that PTEX88 interacts closely with HSP101 but has a weaker affinity with the other core constituents of PTEX. PTEX88 was also found to associate with other PV‐resident proteins, including chaperones and members of the exported protein‐interacting complex that interacts with the major virulence factor PfEMP1, the latter contributing to cytoadherence and parasite virulence. Despite being expressed for the duration of the blood‐stage life cycle, PTEX88 was only discretely observed at the parasitophorous vacuole membrane during ring stages and could not always be detected in the major high molecular weight complex that contains the other core components of PTEX, suggesting that its interaction with the PTEX complex may be dynamic. Together, these data have enabled the generation of an updated model of PTEX that now includes how PTEX88 assembles within the complex. Plasmodium parasites export proteins into their host red blood cell via a translocon called PTEX. Characterization of PTEX88 shows this PTEX component interacts most closely with HSP101 (the putative unfoldase and molecular motor of PTEX), but it also associates with exported protein‐interacting complex, a molecular complex that engages chaperones and interacts with the major virulence factor of Plasmodium falciparum.