Protein folding and stability: What can we learn from high pressure?

Abstract

The relationships between the amino acid sequence of proteins and their structural and functional specificity have yet to be elucidated, as do the determinants for the marginal stability of the folded form of the chain. The mechanisms by which proteins fold and the nature of the rate-determining step in folding remain important questions in the folding field. One important aspect of folded proteins that differentiates them from non-biological polymers is the compactness of their folded structures. Proteins, in fact, are packed as densely as crystals of small organic compounds. Thus the shape of each amino acid plays an important role in providing maximal contacts and interaction free energy within the specific folded structure. Deeper insight into the importance of packing efficiency in defining the form and stability of the folded structure can be gained by probing the volumetric properties of proteins. High pressure as a perturbation of protein structure can give access to such volumetric information concerning equilibrium or transition states in the folding process. The results of pressure denaturation studies must be interpreted in the context of other thermodynamic and kinetic data on protein folding in order to construct a global view of the folding process.

Key Words:

• Key words:Protein folding
• pressure-jump relaxation
• activation volume
• transition state