Conformational detours during folding of a collapsed state.
The protein S6 is a useful model to probe the role of partially folded states in the folding process. In the absence of salt, S6 folds from the denatured state D to the native state N without detectable intermediates. High concentrations of sodium sulfate induce the accumulation of a collapsed state C, which is off the direct folding route. However, the mutation VA85 enables S6 to fold from C directly to N through the transition state TS(C). According to the denaturant dependence of this reaction, TS(C) and C are equally compact, but the data are difficult to deconvolute. Therefore, I have measured the heat capacities (DeltaC(p)) for the D-->C and C-->TS(C) transitions. The DeltaC(p)-values suggest that C needs to increase its surface area in order to fold directly to N. This underlines that it is a misfolded state that can only fold by at least partial unfolding. In contrast to the C-state formed by S6 wildtype, the VA85 C-state is just as compact as the native state, and this may be a prerequisite for direct folding. Individual "gatekeeper" residues may thus play a disproportionately large role in guiding proteins through different folding pathways.
Otzen
Daniel E
DE
Department of Life Sciences, Aalborg University, Sohngaardsholmsvej 49, DK-9000 Aalborg, Denmark. dao@bio.aau.dk
D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008956:Models, Chemical; D009154:Mutation / Q000235:genetics; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D020673:Protein Renaturation; D013696:Temperature; D013816:Thermodynamics; D016963:Thermus thermophilus / Q000737:chemistry* / Q000235:genetics
D001426:Bacterial Proteins