Mimic of photocycle by a protein folding reaction in photoactive yellow protein

The blue light receptor photoactive yellow protein (PYP) displays rhodopsin -like photochemistry based on the trans to cis photoisomerization of its p- coumaric acid chromophore. Here, we report that protein refolding from the acid-denatured state of PYP mimics the last photocycle transition in PYP. T his implies a direct link between transient protein unfolding and photosens ory signal transduction. We utilize this link to study general issues in pr otein folding. Chromophore trans to cis photoisomerization in the acid-dena tured state strongly decelerates refolding, and converts the pH dependence of the barrier for refolding from linear to nonlinear. We propose transitio n state movement to explain this phenomenon. The cis chromophore significan tly stabilizes the acid-denatured state, but acidification of PYP results i n the accumulation of the acid-denatured state containing a trams chromopho re. This provides a clear example of kinetic control in a protein unfolding reaction. These results demonstrate the power of PYP as a light-triggered model system to study protein folding.