Blue light photosensors: Examples of environmentally‐regulated protein/protein interactions

Abstract

Many biological processes are regulated by controlling protein conformation in response to specific environmental cues. This is often mediated by modular protein domains that use environmentally‐triggered changes in bound cofactor conformation or configuration to regulate protein/protein interactions. Photoreceptors exemplify these principles, as they depend on photochemistry mediated by organic chromophores to detect light. In particular, several classes of blue light sensors use flavin chromophores that alter their interactions with the surrounding protein to initiate conformational changes and signaling. We have used solution NMR spectroscopy and other biophysical methods to examine these processes in two classes of photosensory domains.The first of these are Light‐Oxygen‐Voltage (LOV) domains, members of the PAS family of environmental sensors. Illumination generates a covalent protein‐flavin bond within the α/β core of LOV domains, leading to conformational changes in the β‐sheet adjacent to the chromophore. These changes are propagated to non‐canonical protein elements on the other side of this sheet, modifying their function. We will show the generality of this process with data for several classes of LOV‐containing proteins, including serine/threonine kinases, histidine kinases and DNA binding proteins.We will compare these results with parallel studies of BLUF domains (sensors of Blue Light Utilizing FAD), which use different protein topology and photochemistry than LOV domains, but appear to harness light‐induced conformational changes in a similar manner despite these fundamental differences.This work is supported by grants from the NIH (R01 GM081875) and the Robert A. Welch Foundation (I‐1424).