Dr. Catherine Royer
Rensselaer Polytechnic Institute
Monday, April 16, 2018
SSB 7172 @ 3:45 p.m.
Host: Dr. Noham Weinberg
Proteins are dynamic molecules. They undergo conformational transitions on multiple timescales, populating low lying excited states, partially folded states and the unfolded ensemble. These high energy conformers can play important roles in protein function, post-translational modification, turnover and aggregation. It is likely that the structures and relative stabilities of these states have been subject to evolutionary pressure. Given their implication in protein function and homeostasis, it is of interest to characterize the structural and energetic properties of these states. We have used a combination of high pressure and many biophysical techniques, including multi-dimensional NMR, small angle x-ray scattering (SAXS), FTIR, fluorescence, pressure perturbation calorimetry (PPC) and structure based simulations, to map protein folding landscapes. Pressure denatures proteins because the unfolded (and intermediate) states present a smaller molar volume than the folded state. This is due to the existence of internal solvent excluded void volume in folded proteins that is eliminated upon unfolding. The volumetric basis for pressure-induced denaturation is distinct from the basis for chemical denaturation, which depends on the amount of exposed surface area in unfolded states. Hence the conformational ensembles populated via pressure denaturation can be significantly different than those observed in chemical denaturation, providing a more global view of folding landscapes.