![]() Controlling the function of a specific target protein is the goal of a particular sub-category of optogenetics. It uses natural light-sensitive photoreceptors, often ion channels, to artificially induce cellular processes primarily in vivo ( Nagel et al. Probably the most widespread photocontrol method is dubbed optogenetics ( Deisseroth et al. 2017), that is light-sensitive is generated, I will hence refer to it as “photoxenoprotein engineering”. This method has not yet received an official name since here a ncAA-containing protein, or xenoprotein ( Agostini et al. Thus, the receiver, again either a molecular photocage or a photoswitch, is coupled to an amino acid moiety. While photopharmacology primarily uses small-molecular ligands that are attached (non)covalently post translation of the target protein, the second method incorporates a light-responsive non-canonical amino acid (ncAA) into the target protein during translation ( Courtney and Deiters 2018). 2018), which are only activated at the site of the malady thereby reducing side effects. The term originates from the underlying idea to create light-responsive medical drugs targeting mostly key proteins of disease ( Hüll et al. 2014), the receiver consists of a light-responsive molecular cage (photocage) or switch (photoswitch) and is attached to a biologically active moiety. In the first method, dubbed photopharmacology ( Velema et al. Two of the three methods employ light-sensitive small-molecular synthetic receiver compounds and are thus summarized with the term optochemistry ( Ankenbruck et al. Fundamental to each technique are chromophore bearing receiver molecules, which absorb light of specific wavelengths and subsequently undergo different types of reactions. Overview of methods to photocontrol the biological activity of proteins.įor the design of photocontrol in proteins, three major methods have been established ( Figure 1, right box). To this end, light can be applied noninvasively and remotely, as it penetrates tissue in in vivo approaches nanometer to centimeter deep and water-based solutions, e.g., for enzymatic studies or industrial purposes, even meter deep depending on the wavelength of irradiation, and the density and absorption properties of the sample ( Marblestone et al. The dynamic light-mediated regulation of protein function allows to answer fundamental questions and to develop novel tools in organismal, cellular and molecular research ( Figure 1, left box). 2014), as they are key molecules of life and the object of study in various research areas ( Figure 1). One of the most important targets for the implementation of artificial photocontrol are proteins ( Gautier et al. In recent years, this attribute of light was exploited to artificially control diverse biological systems. In particular, light offers dynamic control with a high level of spatiotemporal resolution, which is most paramount for each of these processes. Phototaxis, the migration of microorganisms towards light, phototropism, the growth of plants towards light, photosynthesis, the turnover of light energy into chemical energy as well as vision in animals and humans are only some examples of light-mediated, biological processes. Light plays a decisive role for most forms of life as it stimulates various essential processes in organisms. This review compares the different methods as well as their strategies and current applications for the light-regulation of proteins and provides background information useful for the implementation of each technique. For the targeted design of photocontrol in proteins, three major methods have been developed over the last decades, which employ either chemical engineering of small-molecule photosensitive effectors (photopharmacology), incorporation of photoactive non-canonical amino acids by genetic code expansion (photoxenoprotein engineering), or fusion with photoreactive biological modules (hybrid protein optogenetics). The artificial photocontrol of specifically proteins is of growing interest for the investigation of scientific questions on the organismal, cellular and molecular level as well as for the development of medicinal drugs or biocatalytic tools. In its presence certain proteins inside a cell are excited, which either stimulates or inhibits subsequent cellular processes. Light is essential for various biochemical processes in all domains of life.
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