From snapshot to movie: phi analysis of protein folding transition states taken one step further

Kinetic anomalies in protein folding can result from changes of the kinetic ground states (D, I, and N), changes of the protein folding transition sta te, or both. The 102-residue protein U1A has a symmetrically curved chevron plot which seems to result mainly from changes of the transition state. At low concentrations of denaturant the transition state occurs early in the folding reaction, whereas at high denaturant concentration it moves close t o the native structure, In this study we use this movement to follow contin uously the formation and growth of U1A's folding nucleus by phi analysis. A lthough U1A's transition state structure is generally delocalized and displ ays a typical nucleation-condensation pattern, we can still resolve a seque nce of folding events. However, these events are sufficiently coupled to st art almost simultaneously throughout the transition state structure.