Optimization of protein folding in vivo

We want to understand why proteins are often so unstable and how proteins fold within the cell. To help solve this problem we have devised folding biosensors that link protein folding to antibiotic resistance. These biosensors give us a quantitative and selectable in vivo assay for protein stability. Under antibiotic selection, only stabilized variants grow, making the biosensors an extremely powerful selection for stabilizing proteins. Our approach selects for increased protein stability without any selection for protein function, providing a unique opportunity to separate the contributions of these contrasting forces in the evolution of proteins.

Foit L, Morgan GJ, Kern MJ, Steimer LR, von Hacht AA, Titchmarsh J, Warriner SL, Radford SE, Bardwell JC (2009) Optimizing protein stability in vivo. Mol Cell 36: 861-871. (Pubmed) pdf_icon

This paper was featured by Cell in its “Leading Edge” section (140:5) , was the subject of a preview in Molecular Cell(36:730-31) , an HHMI news story, appeared in Research Highlights in Nature Chemical Biology (6:81) , had a bioessay written about it (BioEssays 32:655-8 ), and was cited as a paper of outstanding interest by Lila Gierasch inCurrent Opinion in Structural Biology 2011, 21:32-41