# Characterization of the ferrous iron transporter Feo

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 2021 · $379,668

## Abstract

The diarrheal disease cholera poses enormous health, economic, and political burdens
worldwide. The causative agent of cholera, Vibrio cholerae, is endemic in aquatic habitats, but it
is capable of infecting the human small intestine, causing a massive, life-threatening diarrheal
response. To colonize the host and cause disease, V. cholerae must acquire essential nutrients,
including iron, in the host environment. The predominant form of iron present in the small
intestine is ferrous iron. Thus, it is critical to understand the mechanisms of ferrous iron uptake
in V. cholerae. The major ferrous iron transporter in V. cholerae is Feo. The Feo system is
widely distributed among all bacterial species, and has important functions in the virulence of
several pathogenic species; nevertheless, very little is known about its structure and mechanism
of transport. In V. cholerae, the Feo transporter is composed of three proteins, FeoA, FeoB,
and FeoC. The membrane-embedded C-terminal domain of FeoB is likely to form the pore for
iron transport, and, interestingly, its N-terminal domain has homology to small eukaryotic G
proteins, suggesting a novel mechanism of transport. The roles of FeoA and FeoC are
unknown. We recently demonstrated that the three Feo proteins associate to form a higher
order complex in vivo. This represents the first structural analysis of the mature, membrane-
embedded, active Feo complex in vivo. The goal of this proposal is to determine the overall
structure of this large complex in order to build and test models for the mechanism of iron
transport. In our first specific aim, we will determine the mass and stoichiometry of the native
Feo complex. This will lay the groundwork for a structural model of the active Feo transporter.
In aim 2, we will refine this model by delineating the sites of interaction within and between the
members of the complex. We will then test the functional significance of these interactions for
complex formation and iron transport activity. In aim 3, we will determine the source of energy
for transport through Feo. These studies will significantly advance our knowledge of the
structure and function of this important and unique iron transporter. Significantly, all our studies
will be carried out using active, membrane-associated Feo complexes in vivo, giving our results
an undeniable relevance over the in vitro studies that currently dominate the Feo field. As our
previous work shows, V. cholerae is an ideal model organism for the study of Feo. We have
already assembled most of the strains and reagents needed, and we, and our collaborators,
have the expertise required to carry out the proposed experiments.

## Key facts

- **NIH application ID:** 10053292
- **Project number:** 5R01AI091957-10
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Shelley M. Payne
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $379,668
- **Award type:** 5
- **Project period:** 2010-12-03 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10053292

## Citation

> US National Institutes of Health, RePORTER application 10053292, Characterization of the ferrous iron transporter Feo (5R01AI091957-10). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10053292. Licensed CC0.

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