"Mapping Protein Folding Landscapes Using High Pressure NMR" Dr. Catherine Royer (Rensselaer Polytechnic Institute)

How and why does pressure unfold proteins? How can we use pressure perturbation to map protein folding landscapes and probe the molecular origins of protein folding cooperativity? We have discovered recently that the major cause for pressure induced unfolding is the elimination of packing defects present in protein folded states. This mechanism, which depends on specific and structurally heterogeneous properties of the folded states of proteins, is distinct from heat and chemical denaturation, the effects of which depend rather homogeneously upon the amount of surface area exposed to solvent in the unfolded states of proteins. This local effect of pressure, in combination with site specific NMR experiments, SAXS, fluorescence, pressure perturbation calorimetry and other biophysical techniques has allowed detailed structural and energetic mapping of protein folding landscapes, and the effects of mutations thereon. We have found for example that single mutations can change a very simple folding pathway into a very complex one with multiple parallel routes. We are currently using pressure coupled with the above mentioned techniques applied to repeat proteins in a systematic study of the sequence and structural determinants of folding cooperativity.

Dr. Royer is the guest of Prof. Jack Kornblatt