Tripartite Biosensors to Assess Protein Stability and Aggregation Propensity in Yeast

Despite the many methods available to study protein folding and aggregation in vitro, there are relatively few tools available to study these processes in the cell. To enable the assessment of protein stability and solubility in vivo, we describe here a biosensor system based on sensitivity to antibiotics that can be used in the cytosol of Saccharomyces cerevisiae. We show an application of the biosensor to determine the in vivo stability or aggregation propensity of stability variants of immunity protein 7, yeast prion proteins Sup35 and Rnq1, as well as the misfolding disease-associated proteins amyloid beta 1-42 (Aβ42) and α-synuclein.