# Structural Characterization of the TOC Protein Translocon Machinery

> **NIH NIH R01** · PURDUE UNIVERSITY · 2021 · $315,579

## Abstract

Project Summary
Infectious diseases cause widespread sickness throughout the world each year and are the second
leading cause of death, particularly in underdeveloped countries. And with the emergence of multi-drug
resistance strains, the necessity for new, more effective, and more sustainable therapies is immediate.
Included in these infectious diseases are the apicomplexa which includes Toxoplasma gondii and
Plasmodium falciparum, the parasites causing toxoplasmosis and malaria, respectively. These parasites
contain a unique plastid-like organelle called an apicoplast which contains four membranes and therefore
have evolved a complex system for importing and exporting proteins across these membranes. These
essential import/export machineries are ideal targets for novel antibiotics against these pathogens. Many
of these translocon machineries are also conserved in other higher eukaryotic organelles such as
chloroplasts and mitochondria, where a large majority of genes are nuclear encoded and therefore must
be imported post-translationally. One such machinery is the conserved translocon of the outer membrane
in chloroplasts (TOC) complex from Arabidopsis thaliana, a model system for studying chloroplast biology.
The TOC complex consists of primarily three components, Toc33/34 and Toc159, both GTPases
containing an N-terminal transmembrane helix anchoring them into the outer membrane, and Toc75, a 16-
stranded β-barrel membrane-spanning translocon. While mechanistic models have been put forth for how
the TOC complex functions, they have remained largely unproven due to the lack of structural
characterization, which is needed to stitch together all the pieces of the mechanistic puzzle. In our studies,
we will use biophysical methods, X-ray crystallography, cryo-electron microscopy, and small-angle X-ray
scattering to structurally and functionally characterize this specialized machinery. Our results will fill a
longstanding gap in the field and will be essential for piecing together the mechanism for how the TOC
complex functions in protein import in apicomplexa and chloroplasts.

## Key facts

- **NIH application ID:** 10135111
- **Project number:** 5R01GM127896-04
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Nicholas Noinaj
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $315,579
- **Award type:** 5
- **Project period:** 2018-05-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135111

## Citation

> US National Institutes of Health, RePORTER application 10135111, Structural Characterization of the TOC Protein Translocon Machinery (5R01GM127896-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10135111. Licensed CC0.

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