New Paper!

In a new paper, we use the endogenous E. coli metalloprotease PepQ to test predictions of both passive and active models of GroELS-stimulated folding. 

While GroELS increases the folding rate of PepQ by over 15-fold, using both ensemble and single-molecule fluorescence techniques, we show that slow spontaneous folding of PepQ is not caused by aggregation. In addition, our fluorescence measurements suggest that, when folding inside the GroEL-GroES cavity, PepQ populates conformations not observed during spontaneous folding in free solution. Using cryo-electron microscopy, we show that the GroEL C-termini make physical contact with the PepQ folding intermediate and help retain it deep within the GroEL cavity, resulting in reduced compactness of the PepQ monomer. 

Our findings strongly support an active model of chaperonin-mediated protein folding, where partial unfolding of misfolded intermediates plays a key role.

Department of Biochemistry and Biophysics                           Texas A&M University              2018