From photon to biological signaling: emerging principles in the biophysical mechanism of photoreceptor activation

Photosensory proteins convert photon absorbance into protein conformational changes that initiate biological signaling. Six distinct classes of photoreceptors with diverse folds, chromophores, and initial photochemical events have been studied in detail. We analyzed results for well-studied members of each of these photoreceptors to identify emerging trends in the molecular mechanism of their function. First, the primary photochemical event usually occurs on an ultrafast time scale and involves only very small atomic motions limited to the light-absorbing chromophore. A key question is how these ultrafast, localized conformational changes trigger large-amplitude, long-lived conformational changes for signaling. Time-resolved studies show that in all six receptor types the initial photochemical event is followed by much slower intramolecular proton transfer, and subsequently by large protein conformational changes. A dual role for these proton transfer events is emerging, causing changes in hydrogen bonding in some photoreceptors and changes in electrostatics in others, which then drive conformational changes for receptor activation. These results provide a broad mechanistic and energetic framework for dissecting the mechanism of photoreceptor function.