A natural missing link between activated and downhill protein folding scenarios
Literature Information
Feng Liu, Caroline Maynard, Gregory Scott, Artem Melnykov, Kathleen B. Hall
We propose protein PTB1∶4W as a good candidate for engineering into a downhill folder. PTB1∶4W has a probe-dependent thermal unfolding curve and sub-millisecond T-jump relaxation kinetics on more than one time scale. Its refolding rate in denaturant is a non-linear function of denaturant concentration (curved chevron plot). Yet at high denaturant concentration its unfolding is probe-independent, and the folding kinetics can be fitted to a single exponential decay. The domain appears to fold via a mechanism between downhill folding and activated folding over several small barriers, and when denaturant is added, one of these barriers greatly increases and simplifies the observed folding to apparent two-state kinetics. We predict the simplest free energy function consistent with the thermal denaturation and kinetics experiments by using the singular value Smoluchowski dynamics (SVSD) model. PTB1∶4W is a natural ‘missing link’ between downhill and activated folding. We suggest mutations that could move the protein into the downhill folding limit.
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