U.S. Department of Energy

Pacific Northwest National Laboratory

To Better Understand Protein Modifications is to Better Understand Biological Processes

Redox signaling.

The Science                      

In this paper, the authors describe how and why a form of quantitative proteomics they call redox proteomics could be  an indispensable tool for redox biology, which investigates cellular oxygen levels. Quantitative proteomics as a whole, they say, provides valuable insight into cell signaling, which affects biological processes that are involved in human health. But there’s room for improvement. “We’re always looking for scientific approaches that provide enhanced sensitivity, specificity, and coverage in the field of proteomics,” said redox proteomics advocate and lead author Wei-Jun Qian, a bioanalytical chemist at the Pacific Northwest National Laboratory (PNNL).  In the paper he and co-authors also consider proteomic sample processing, chemical or affinity enrichment strategies, and quantitative approaches. .

The Impact

This paper reviews recent advances in quantitative proteomic approaches for investigating post-translational modifications (PTMs) of the kind of oxidation on specific protein amino acid residues (known as “redox,” in scientific shorthand).  PTMs are important components in cell signaling. The more we know about them, the more we understand biological processes, including those associated with disease states in humans. 

Summary

The tiniest of cells communicate with each other via signals that trigger biological processes in our bodies. In proteins, these signals are greatly affected by the biochemical reactions known as post-translational modifications, or PTMs. In addition, there is biological significance in redox PTMs as markers of both healthy and disease states.

“Redox” is scientific shorthand for reduction-oxidation reaction. That is when the oxidation states of atoms are changed by losing or gaining electrons. Redox processes are fundamental in all levels of biology.

Quantitative proteomics can help researchers characterize PTMs, but there’s a need for new approaches (such as redox proteomics) that more broadly quantify relative changes for specific types of PTMs. 

New approaches have been developed to help identify reversible and irreversible redox PTMs. Reversible modifications are those that researchers can affect once they detect them. Irreversible modifications, on the other hand, are pathological markers of oxidative stress and cannot be chemically altered. Redox proteomics is promising for identifying novel redox-controlled molecular targets for early interventions to prevent the development of pathologies. 

Redox proteomics is a relatively new field of study. But development of quantitative proteomics technologies and approaches that provide enhanced sensitivity, specificity, and coverage, there is potential for great discoveries. 

Funding

Portions of the work were supported by grants from the National Institutes of Health. The experimental work described herein was performed in the Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, a national scientific user facility sponsored by the U.S. Department of Energy.

Publications

Jicheng Duan, et al., “Quantitative proteomic characterization of redox-dependent post-translational modifications on protein cysteines.” Molecular Biosystems(2017). DOI: 10.1039/c6mb00861e.

Date: 
May 2017
| Pacific Northwest National Laboratory