ALL-OR-NONE SOLVENT-INDUCED TRANSITIONS BETWEEN NATIVE, MOLTEN GLOBULE AND UNFOLDED STATES IN GLOBULAR-PROTEINS

Background: It has long been established that temperature-induced melt ing of small globular proteins is an all-or-none transition. Little wa s known, however, about the degree of cooperativity of denaturant-indu ced transitions in proteins, especially in those cases in which the pr oteins unfold through the molten globule state. Results: We have proce ssed data on the equilibrium urea-induced and guanidinium chloride (Gd mCl)-induced unfolding of globular proteins from the native to the unf olded state, from the native to the molten globule stale and from the molten globule to the unfolded state. We show that in ail these cases, the cooperativity of unfolding increases linearly with the increase o f the molecular weight of the protein up to 25-30 kDa. Conclusions: Th e cooperative unit of the urea-induced and GdmCl-induced equilibrium t ransitions of small proteins between the native, molten globule and un folded states includes the protein molecule as a whole. In other words , both native and molten globule proteins are unfolded by strong denat uring solvents according to an all-or-none mechanism.