Compact intermediate states in protein folding.

The number of observations of both stable and transient partially folded intermediates is now sufficient for us to assume that all proteins, under the appropriate conditions, will form such species. These intermediates are characterized by substantial secondary structure and little tertiary structure; a collapsed conformation more compact than the unfolded state; exposed hydrophobic surfaces, which lead to binding of hydrophobic dyes and a propensity to aggregate; and a heat capacity similar to that of the unfolded state. The term compact intermediates encompasses a broad range of conformations and degrees of folding and compactness: compact intermediates have no single, unique conformation, but rather a whole plethora of structures that range from being very similar to the native state to being substantially expanded and significantly unfolded. The properties of compact intermediates from different proteins, and in some cases from the same protein under different conditions, may be significantly different. Equilibrium compact intermediates may be good models for transient intermediates formed during folding.