Photoactive Yellow Protein, a new type of photoreceptor protein: Will this "yellow lab" bring us where we want to go?

Photoactive Yellow Protein (PYP), discovered almost 20 years ago in Ectothiorhodospira (Halorhodospira) halophila,(1) is a 4-hydroxycinnamic acid-containing protein that functions as a blue-light photoreceptor in a behavioral avoidance response in this organism. During the past 10 years, PYP has become a model system for studies in photochemistry and protein folding, to the extent that it has become competitive with the rhodopsins. This is because PYP is small and very water-soluble, forms crystals readily (diffracting to high resolution), and shows excellent chemical- and photo-stability. These overall characteristics have allowed the application of an array of physicochemical techniques to analyze the biological function of PYP, i.e., the translation of a change of the configuration of its 4-hydroxycinnamic acid chromophore into an altered conformation of the surrounding protein. This has led to detailed insight into this process, both temporally and spatially, with respect to the structure of the transient intermediates involved, although we are still quite far from being able to track the position of all atoms in space, upon light activation of the protein in the relevant time domain. Nevertheless, the data already obtained may function as a calibration set in future work, to extend the time span of molecular dynamics simulations of conformational transitions in proteins to the time scale relevant for catalytic turnover. Occasionally, the application of multiple biophysical techniques has led to (seemingly) conflicting results. In one example, this has revealed the fact that the light-induced conformational transitions in this photoreceptor protein can become restricted by the mesoscopic context, e.g., via a crystal lattice. Other inconsistencies, such as those regarding the radius of gyration of the protein, still remain to be explained. Below, we discuss the spatial and temporal details of the series of steps initiated in PYP by a short pulse of blue light, as revealed with this array of biophysical techniques, thereby highlighting contributions from our own group.