It's a two-way street: Photoswitching and reversible changes of the protein matrix in photoswitchable fluorescent proteins and bacteriophytochromes.

Chromophore-bearing proteins that are (reversibly) altered after light illumination are major functional components of nature. They gained considerable attention in the last decades since the dynamic interactions of the chromophore and protein matrix can be used to control downstream effects altering the functionality of proteins, cells, or complete organisms with light (optogenetics). Additionally, the photophysical effects can be employed to add capabilities to optical imaging. For example, light can be used to reversibly switch the signal on or off (e.g., fluorescence). In this article, we review chromophore and protein matrix interactions, focusing on photoswitching fluorescent proteins of the GFP family (RSFPs) and natively photoswitching bacteriophytochromes (BphPs). This review aims to provide an in-depth understanding of the dynamic interplay between photoswitching photophysics and the protein matrix and a thorough discussion on how this connection has been harnessed for the development of optogenetic and imaging tools.