# Structure and Function of DcrB, an Enterobacterial Copper Resistance Protein

> **NIH NIH R15** · UNIVERSITY OF WISCONSIN LA CROSSE · 2024 · $401,680

## Abstract

Project Summary
 Copper ions are an essential nutrient for living organisms and are widely used in enzyme-catalyzed redox
reactions. However, high levels of copper ions are toxic to cells, including microbial pathogens. Healthcare
facilities use copper in touched surfaces to prevent the spread of infectious diseases, and mammalian immune
systems can harness the toxicity of copper ions to kill pathogenic bacteria in macrophages. Nevertheless,
pathogenic bacteria can resist being killed by copper ions. Therefore, this proposal seeks to understand
structure-function relationships for a novel copper ion resistance protein in enterobacteria, a family of
Gram-negative bacteria that includes major etiological agents of food-borne illness and hospital-acquired
infections worldwide. Our preliminary studies have shown that the lipoprotein DcrB confers resistance to high
Cu2+ in Salmonella enterica serovar Typhimurium, a bacterial cause of food-borne illness in humans. The
DcrB protein is highly conserved in enterobacteria. We have determined the first three-dimensional structure
of a DcrB protein, which revealed it contains the Mog1p/PsbP-like fold, a widespread fold found in proteins that
participate in a range of cellular functions. We have identified structural features that are important for the
function of DcrB in copper resistance.
 This proposal seeks to understand how these features of DcrB are essential for its function. Aim 1 focuses
on determining how two clusters of residues form an essential functional combination. Aim 2 focuses on
investigating how the N-terminal beta-hairpin is essential for the function of DcrB. For both aims, we will use
site-directed mutagenesis, genetic, and physiological experiments to probe the structural and biochemical
properties for each feature. We will use X-ray crystallography to determine how changes to these features
impact the structure of DcrB, and we will use biophysical experiments to investigate the influence of these
features on the thermodynamics of folding of DcrB.
 The proposed research will engage undergraduate students at a primarily undergraduate institution in
hands-on biomedical research that will reveal how a novel family of membrane-anchored proteins contributes
to copper ion resistance in a medically relevant bacterial species. Results will be applicable to various human
pathogens that cause bacterial food-borne illness, plague, and healthcare-associated infections. Knowledge
gained from this research will lead to the development of strategies to target bacterial resistance to metal ions
and enhance the effective use of copper as an antimicrobial surface. Broadly, this proposal will 1) provide
insight into the fundamental biological question of how cells control levels of a toxic metal ion; 2) advance
structure-function knowledge for a widespread protein fold; 3) impact human health research by studying this
question in bacteria that threaten public health worldwide; and 4) impact scientific ed...

## Key facts

- **NIH application ID:** 10793134
- **Project number:** 1R15GM152892-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN LA CROSSE
- **Principal Investigator:** John May
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $401,680
- **Award type:** 1
- **Project period:** 2024-02-15 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10793134

## Citation

> US National Institutes of Health, RePORTER application 10793134, Structure and Function of DcrB, an Enterobacterial Copper Resistance Protein (1R15GM152892-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10793134. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*