Tripping the Light Fantastic: Blue-Light Photoreceptors as Examples of Environmentally Modulated Protein−Protein Interactions

Abstract

Blue light photoreceptors play a pivotal role in detecting the quality and quantity of light in the environment, controlling a wide range of biological responses. Several families of blue-light photoreceptors have been characterized in detail using biophysics and biochemistry, beginning with photon absorption, through intervening signal transduction, to regulation of biological activities. Here we review the Light Oxygen Voltage (LOV), Cryptochrome (CRY) and sensors of Blue Light Using FAD (BLUF) families, three different groups of proteins that offer distinctly different modes of photochemical activation and signal transduction, yet play similar roles in a vast array of biological responses. We cover mechanisms of light activation and propagation of conformational responses that modulate protein:protein interactions involved in biological signaling. Discovery and characterization of these processes in natural proteins are now enabling the design of photoregulatable engineered proteins, facilitating the generation of novel reagents for biochemical and cell biological research.

Transient conformational fluctuation of TePixD during a reaction

“…This result implies that the compressibility changes during the reaction. From the pressure dependence of the amplitude, the compressibility change of two short-lived intermediate (I 1 and I 2 ) states were determined to be +(5.6 ± 0.6) × 10 −2 cm 3 ·mol −1 ·MPa −1 for I 1 and +(6.6 ± 0.7)×10 −2 cm 3 ·mol −1 ·MPa −1 for I 2 . This result showed that the structural fluctuation of intermediates was enhanced during the reaction.…”

“…Photosensor proteins are an important example. They have light-sensing domains and function by using the light-driven changes in domain-domain interactions (1). The sensor of blue light using FAD (BLUF) domain is a light-sensing module found widely among the bacterial kingdom (2).…”

Resolving cryptic aspects of cryptochrome signaling

“…Photolyase activation involves two cofactors, the catalytic FAD in a two-electron reduced FADH-state and an antennae cofactor that can vary in identity (i.e., MTHF, HDF, flavins). Activation of photolyases is achieved by absorption of UV-A light by the antennae cofactor, which induces electron transfer from FADHto the DNA lesion (3,8). Importantly, a second electron transfer pathway exists in photolyases and is composed of a series of three Trp residues (Trp triad) forming a pathway from the catalytic FAD to the protein surface (Fig.…”

“…These debates center on sequence conservation within the CRY/ photolyase family (CPF). Despite high sequence similarities, CPF members demonstrate functions ranging from DNA repair enzymes (photolyases) to blue light-regulated growth, development, and circadian rhythms in diverse organisms (CRYs) (3). In all cases, CPF function hinges upon a bound flavin adenine dinucleotide (FAD) cofactor that undergoes interconversion between several redox states (Fig.…”

“…1). Currently, the nature of the ground and excited states of FAD, the presence and role of secondary pigments, and the requirement of a conserved sequence of three Trp residues (Trp triad) remain controversial (3,4). Debates stem from the difficulties of resolving contradictions between in vitro photochemical experiments and in vivo biological function (4).…”