Protein folding is usually driven by the hydrophobic core while the role of the surface residues is considered to be marginal. Intimately ligated to protein folding, protein stability establishes the energy required to unfold a protein and the equilibrium populations of the folded and unfolded conformations at a given temperature. Proteins from halophilic organisms challenge this concept since they are often unfolded at low salt conditions while they become folded only in the presence of high salt concentrations. This is possible thanks to a severe modulation of the amino acid composition in the surface of the protein. This halophilic signature is general and conserved and constitutes a biological meter for protein quinary structure (the protein stability and folding when considering the cosolute).
In here, we use NMR spectroscopy and other biophysical techniques to investigate the mechanisms contributing to protein haloadaptation (i. e. stabilization in KCl) and their potential interplay with the stabilization mechanism induced by osmolytes (Sarcosine, Taurine, TMAO, Sucrose, Glycine, Betaine and Trehalose), using several halophilic and mesophilic proteins as reporters. Our data suggest co-evolution of the surface residues to become stabilized not only by salt, but also by osmolytes as well.