Plasmodium falciparum SURFIN_4.1 forms an intermediate complex with PTEX components and Pf113 during export to the red...

Area of Science:

• Molecular parasitology
• Infectious disease mechanisms
• Protein translocation

Background:

• Plasmodium falciparum exports hundreds of proteins into red blood cells (RBCs) to facilitate parasite growth.
• The Plasmodium translocon of exported proteins (PTEX) complex mediates protein export across the parasitophorous vacuole (PV) membrane.
• The precise molecular machinery for translocating integral membrane proteins via PTEX remains incompletely understood.

Purpose of the Study:

• To investigate the molecular composition of the PTEX translocation complex for integral membrane proteins.
• To elucidate the role of the uncharacterized protein Pf113 in protein translocation.
• To characterize the translocation intermediate complex at the parasite plasma membrane.

Main Methods:

• Utilized a mini-SURFIN4.1 construct, representing key domains of an exported integral membrane protein.
• Investigated protein interactions within the PTEX complex using biochemical assays.
• Employed an inducible translocon-clogged system to trap translocation intermediates.

Main Results:

• Mini-SURFIN4.1 forms a translocation intermediate complex with core PTEX components (EXP2, HSP101, PTEX150).
• The protein Pf113, localized to dense granules and parasite periphery, was found exposed to the PV space.
• A stable translocation intermediate complex at the parasite plasma membrane contained EXP2 and processed Pf113.

Conclusions:

• Pf113 is implicated in the translocation of integral membrane proteins like SURFIN4.1.
• These findings provide new insights into the mechanisms of Plasmodium protein export, particularly for membrane proteins.
• Understanding these pathways is crucial for developing new antimalarial strategies.