The Action of Chemical Denaturants: From Globular to Intrinsically Disordered Proteins

Abstract

Proteins perform their many functions by adopting either a minimal number of strictly similar conformations, the native state, or a vast ensemble of highly flexible conformations. In both cases, their structural features are highly influenced by the chemical environment. Even though a plethora of experimental studies have demonstrated the impact of chemical denaturants on protein structure, the molecular mechanism underlying their action is still debated. In the present review, after a brief recapitulation of the main experimental data on protein denaturants, we survey both classical and more recent interpretations of the molecular basis of their action. In particular, we highlight the differences and similarities of the impact that denaturants have on different structural classes of proteins, i.e., globular, intrinsically disordered (IDP), and amyloid-like assemblies. Particular attention has been given to the IDPs, as recent studies are unraveling their fundamental importance in many physiological processes. The role that computation techniques are expected to play in the near future is illustrated.

Fluorescence-Based Protein Stability Monitoring—A Review

“…Different denaturants have different mechanism of action, and thus, some proteins are more tolerant to one denaturant than to others. Guanidine salts, especially GdnHCl and guanidine thiocyanate, are commonly used denaturants, as well as urea, which is a nonionic and milder alternative for denaturation [163,164]. These denaturants can also be used as ultra-strong thiourea, but also, milder options like alcohols and pH have been used [165][166][167].…”