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Chemoproteomic Profiling Maps Zinc-Dependent Cysteine Reactivity
Nan Qiu1,2, Dany Pechalrieu1, Daniel Abegg1
1Department of Chemistry, University of Illinois Chicago, 845 W Taylor St., Chicago, Illinois 60607, United States.
This study introduces a new chemical proteomics method to identify zinc-sensitive proteins by profiling cysteine reactivity. The findings reveal how zinc impacts protein function, offering insights into zinc-related health disorders.
Area of Science:
- Biochemistry
- Proteomics
- Molecular Biology
Background:
- Zinc is an essential micronutrient crucial for protein structure, function, and signaling.
- Altered zinc homeostasis is linked to various health disorders, highlighting the need to understand its molecular mechanisms.
- Identifying zinc-regulated proteins and their modifications is challenging but vital for advancing zinc biology.
Purpose of the Study:
- To develop a quantitative chemical proteomics platform for profiling protein cysteine reactivity.
- To identify and characterize zinc-sensitive proteins and their proteoforms.
- To elucidate the molecular mechanisms underlying zinc's regulation of biological processes.
Main Methods:
- Development of a quantitative chemical proteomics platform.
- Utilizing a protein-conjugated resin for selective zinc (Zn2+) removal from cell culture media.
- Global profiling of proteinaceous cysteine reactivities following cellular zinc depletion.
Main Results:
- Identification of numerous zinc-sensitive cysteines on proteins with diverse functions.
- Demonstration that zinc depletion increases cysteine reactivity.
- Evidence of zinc's regulatory role in the enzymatic activities, post-translational modifications, and subcellular localization of proteins like PRDX6, PAFAH1B3, and PGK1.
Conclusions:
- The developed proteomics platform effectively identifies zinc-regulated proteins.
- Zinc directly modulates protein function through cysteine interactions.
- This research provides a foundation for understanding zinc's role in health and disease at a molecular level.
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