Conformational and Disorder to Order Transitions in Proteins: Structure / Function Correlation in Apolipoproteins

The concept of protein folding is directly related with the process of reversible disorder-toorder transitions, by which an unfolded polypeptide chain folds into a specific functional native structure (Eaton et al., 2000; Rose et al., 2006). For folding into a native state, unfolded polypeptide chains require the intervention of weak interactions. Driven by hydrophobic interactions, a polypeptide chain begins to fold when placed in an aqueous medium, and rapidly becomes a molten globule followed by an important release of latent heat. Stabilization of the molten globule is achieved mainly through the distribution of hydrophobic residues away from the water matrix. On the other hand, because the polar residues contained in a protein develop hydrogen bonds with the water network as well as with each other, α-helices and β-sheets can be formed when bonds switch between molecules. It has been calculated that such bonds might be in the order of 10-12 s, very similar to those we find in water itself. The random equilibrium can be shifted toward one of these conformations by means of two stages: a fast stage, during which the unfolded polypeptide becomes a molten globule; and a slow stage, in which the molten globule slowly transforms into a fully folded form or native state (Huang, 2005). These two stages in protein folding can be illustrated by a ‘‘folding funnel’’, during which due to a small change in entropy with a large loss of energy, a molten globule evolves into the native state (Fig. 1a) (Dobson, 2003; Gsponer & Vendruscolo, 2006).