Chapter 4 - Proteome-scale studies of protein stability

Abstract

Proteome stability is required to ensure proper function of cells and organisms. Its disturbance is at the core of clinically relevant abnormal cellular states, such as tumorigenic transformation, neurodegeneration, and aging. Current technical possibilities in the field of the quantitative mass spectrometry (MS) of proteins allow studying the proteome-wide aggregation and degradation of proteins under different stress and pathologic conditions. In addition to the biological readouts of protein destabilization, several methods have been developed to test conformational changes of polypeptides on the proteome scale. Finally, direct analysis of protein stability and biophysical characterization of protein folding and ligand binding can be achieved on the proteome scale. The proteomic studies of protein stability have significant novelty potential in basic and applied biomedical research. Several important areas of their application have ensured an increasing interest and significant advances in the respective MS-based approaches.