Molecular eyes: proteins that transform light into biological information

Abstract

Most biological photoreceptors are protein/cofactor complexes that induce a physiological reaction upon absorption of a photon. Therefore, these proteins represent signal converters that translate light into biological information. Researchers use this property to stimulate and study various biochemical processes conveniently and non-invasively by the application of light, an approach known as optogenetics. Here, we summarize the recent experimental progress on the family of blue light receptors using FAD (BLUF) receptors. Several BLUF photoreceptors modulate second messenger levels and thus represent highly interesting tools for optogenetic application. In order to activate a coupled effector protein, the flavin-binding pocket of the BLUF domain undergoes a subtle rearrangement of the hydrogen network upon blue light absorption. The hydrogen bond switch is facilitated by the ultrafast light-induced proton-coupled electron transfer (PCET) between a tyrosine and the flavin in less than a nanosecond and remains stable on a long enough timescale for biochemical reactions to take place. The cyclic nature of the photoinduced reaction makes BLUF domains powerful model systems to study protein/cofactor interaction, protein-modulated PCET and novel mechanisms of biological signalling. The ultrafast nature of the photoconversion as well as the subtle structural rearrangement requires sophisticated spectroscopic and molecular biological methods to study and understand this highly intriguing signalling process.

Role of active site conformational changes in photocycle activation of the AppA BLUF photoreceptor

“…BLUF proteins are critical for processes such as the light regulation of photosynthetic gene expression, phototaxis, and photophobia in bacteria (8). These proteins are unique among the photoreceptor proteins in that they exhibit photoinduced PCET and thus are powerful model systems for the investigation of this charge-transfer process in a protein environment.…”

“…Despite numerous experimental and computational studies (8,(13)(14)(15)(16)(17), the exact nature of the signaling state and the mechanism of long-range signaling in BLUF proteins are not well understood. The active site conformation in even the dark-adapted state is still under debate because of discrepancies in the orientations of the key active site Trp, Met, and Gln residues among different experimental crystal and solution structures of BLUF domains (18)(19)(20)(21)(22)(23)(24)(25)(26).…”

Synapses in the spotlight with synthetic optogenetics

“…In contrast to optogenetic tools incorporating naturally occurring chromophores, this method employs synthetic , light‐sensitive photoswitches . Akin to chromophores found in nature (e.g., retinal ), photoswitches too undergo chemical reactions following the absorption of specific wavelengths. One highly relevant reaction to the design of biological tools is the trans ‐to‐ cis isomerization of azobenzenes, resulting in a large geometrical change and significant reduction in the length of the molecule (Fig A) .…”

Light based cellular interactions: hypotheses and perspectives

“…Some pathways are already known [49,55,74]. We hope that this model inspires researchers to look at and for integrated pathways of photoreceptors.…”

“…To have effective receivers, we need biochemical compounds which can absorb light (also known as photoreceptors containing a chromophore) and have one or more aromatic components [53,55]. We will now see that these required components are present in cells.…”