# Specificity of Plasmodium falciparum protein export

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2022 · $236,250

## Abstract

The malaria parasite Plasmodium falciparum exports several hundred
proteins into its host cell to modulate nutrient uptake, infected RBC biophysical
properties, adherence to vascular endothelium and host immune response. These
exported protein effectors are synthesized in the parasite ER, traverse the
secretory system and are then translocated from the parasitophorous vacuole (PV)
into the host RBC. Most have a protein export element (PEXEL) that is essential
for the export process but is cleaved co-translationally by the aspartic protease
plasmepsin V. How the processed protein is recognized for export is not at all clear.
Certain mutations in the mature N-terminus of PEXEL-containing reporter
constructs can prevent export, but changing the mature N-terminus to all alanines
does not impair export. We hypothesize that export is the default pathway for
secretory proteins and that specific mutations block export or promote PV retention.
We posit that these mutations dictate recognition by a chaperone. To establish this
model, we must identify the chaperone(s) that confer specificity.
To address these questions, Aim 1 will focus on the protein machinery that
mediates export specificity. Export-destined and PV retained proteins will be pulled
down from the PV and from the ER. Comparative proteomic analysis will be
employed to identify key components of the export pathway. Proximity biotinylation
will comprise a second approach to this analysis. Candidate interacting proteins
will be validated in reciprocal pulldowns. This will pave the way for future reverse
genetic and biochemical assessments. We anticipate that the proposed studies
will yield great insight into the mechanism of protein export that is so important to
the pathogenesis of malaria. We hope that this work will point the way to new
therapies for this devastating disease.

## Key facts

- **NIH application ID:** 10508060
- **Project number:** 1R21AI171062-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Daniel E. Goldberg
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $236,250
- **Award type:** 1
- **Project period:** 2022-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10508060

## Citation

> US National Institutes of Health, RePORTER application 10508060, Specificity of Plasmodium falciparum protein export (1R21AI171062-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10508060. Licensed CC0.

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