# Structural and functional analysis of novel microbial membrane export proteins

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $46,683

## Abstract

Project Summary/Abstract:
Microbes have contended with numerous and unusual chemical threats throughout evolutionary time—and in
response have evolved a catalogue of specialized membrane export proteins to deal with hostile elements.
Two particularly pernicious xenobiotics are fluoride ion and guanidinium ion. Both ions are common in the
microbial milieu, and because of their resemblance to common metabolites, these ions have broad-spectrum
inhibitory effects on metabolism in the absence of membrane exporters. This proposal addresses two
different, novel families of membrane proteins, the Gdx and Fluc families, which protect bacteria by exporting
guanidinium and fluoride ion, respectively. I have identified and characterized the functions of these previously
unannotated proteins, and I have solved the x-ray crystal structure of a representative Fluc protein. I now
propose to functionally and structurally characterize them using a variety of tools including electrophysiology,
membrane protein biochemistry, and x-ray crystallography. Since these two proteins are among the smallest
and simplest membrane transport proteins known, they are particularly good model systems to probe
fundamental aspects of membrane transport proteins that are currently poorly understood, for example, the
molecular mechanism of anion transport and selectivity, membrane protein biogenesis and folding, and
substrate-coupled conformational change. In addition, gaining a molecular understanding of how these
proteins recognize and selectively export their substrates will pave the way for the development of novel
antibiotics targeting export of ubiquitous, toxic environmental ions.

## Key facts

- **NIH application ID:** 10064038
- **Project number:** 3R35GM128768-02S1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Randy B. Stockbridge
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $46,683
- **Award type:** 3
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10064038

## Citation

> US National Institutes of Health, RePORTER application 10064038, Structural and functional analysis of novel microbial membrane export proteins (3R35GM128768-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10064038. Licensed CC0.

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