Folding of a bacterial protein is directly related to signal transduction, and temporary partial unfolding can be a mechanism of signaling, according to researchers at the University of Chicago.

Wouter Hoff and his colleagues study photoactive yellow protein (PYP), a circadian photoreceptor from purple bacteria. They found that when PYP absorbs light it switches from the off (trans chromophore) to the on (cis chromophore) conformation, where it is partially unfolded. “The result we obtained,” he says, “is that the switch in this case is based on temporary unfolding of the protein.” Hoff suggests that a similar switch might be operating in other signal transduction systems.

The findings have some immediate applications. Investigators have had difficulty determining whether a particular intermediate for folding is a productive on-pathway intermediate that will result in a proper conformation, or whether something has gone wrong during folding. With PYP, folding by rapid mixing in denaturants and refolding after signaling both pass through the same state, suggesting that this is an on-pathway intermediate.

PYP could also improve time resolution for protein-folding studies. Rapid mixing experiments are usually limited to 1 ms resolution, but the light-triggered nature of PYP refolding should cut that down to nanoseconds. ▪


Lee, B-C., et al
Proc. Natl. Acad. Sci. USA.