Optogenetics is an emerging bioengineering technology that has been rapidly developed in recent years by cross-integrating optics, genetic engineering, electrophysiology, software control, and other disciplines. Since the first demonstration of the millisecond neuromodulation ability of the channelrhodopsin-2 (ChR2), the application of optogenetic technology in basic life science research has been rapidly progressed, especially in neurobiology, which has driven the development of the discipline. As the optogenetic tool protein, microbial rhodopsins have been continuously explored, modified, and optimized, with many variants becoming available, with structural characteristics and functions that are highly diversified. Their applicability has been broadened, encouraging more researchers and clinicians to utilize optogenetics technology in research. In this review, we summarize the species and variant types of the most important class of tool proteins in optogenetic techniques, the microbial rhodopsins, and review the current applications of optogenetics based on rhodopsin qualitative light in biology and other fields. We also review the challenges facing this technology, to ultimately provide an in-depth technical reference to support the application of optogenetics in translational and clinical research.
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http://dx.doi.org/10.3389/fnins.2022.966772 | DOI Listing |
J Photochem Photobiol B
January 2025
All-Russian Collection of Microorganisms (VKM), G.K. Skryabin Institute of Biochemistry and Physiology of Microorganisms, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, pr. Nauki 5, 142290 Pushchino, Moscow Region, Russia.
In recent decades, most studies of microbial rhodopsins have focused on their identification and characterization in aquatic bacteria. In 2021, actinomycetes of the family Geodermatophilaceae, commonly inhabiting terrestrial ecosystems in hot and arid regions, have been reported to contain rhodopsins with DTEW, DTEF and NDQ amino acid motifs. An advanced bioinformatics analysis performed in this work additionally revealed NTQ rhodopsin and heliorhodopsins.
View Article and Find Full Text PDFJ Phys Chem B
December 2024
Aix Marseille Univ, CNRS, ICR, 13013 Marseille, France.
The automatic rhodopsin modeling (ARM) approach is a computational workflow devised for the automatic buildup of hybrid quantum mechanics/molecular mechanics (QM/MM) models of wild-type rhodopsins and mutants, with the purpose of establishing trends in their photophysical and photochemical properties. Despite the success of ARM in accurately describing the visible light absorption maxima of many rhodopsins, for a few cases, called outliers, it might lead to large deviations with respect to experiments. Applying ARM to rhodopsin (GR), a microbial rhodopsin with important applications in optogenetics, we analyze the origin of such outliers in the absorption energies obtained for GR wild-type and mutants at neutral pH, with a total root-mean-square deviation (RMSD) of 0.
View Article and Find Full Text PDFJ Phys Chem B
December 2024
Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1/3, Moscow 119991, Russia.
The primary photoisomerization reactions of the all- to 13- and 11- to all- retinal protonated Schiff base (RPSB) in microbial and animal rhodopsins, respectively, occur on a subpicosecond time scale with high quantum yields. At the same time, the isolated RPSB exhibits slower excited-state decay, in particular, in its all- form, and hence the interaction with the protein environment is capable of changing the time scale as well as the specificity of the reaction. Here, by using the high-level QM/MM calculations, we provide a comparative study of the primary photoresponse of and RPSB isomers in both the initial forms and first photoproducts of microbial rhodopsin 2 (KR2) and bacteriorhodopsin (BR), and animal visual rhodopsin (Rho).
View Article and Find Full Text PDFChem Sci
January 2025
University of Strasbourg, CNRS, IPCMS 23 Rue du Loess 67034 Strasbourg France
Archaerhodopsin-3 (AR-3) variants stand out among other rhodopsins in that they display a weak, but voltage-sensitive, near-infrared fluorescence emission. This has led to their application in optogenetics both in cell cultures and small animals. However, in the context of improving the fluorescence characteristics of the next generation of AR-3 reporters, an understanding of their ultrafast light-response in light-adapted conditions, is mandatory.
View Article and Find Full Text PDFFront Mol Biosci
November 2024
Institut de Biologie Structurale J.-P. Ebel, Université Grenoble Alpes-CEA-CNRS, Grenoble, France.
The primary goal of our work is to provide structural insights into the influence of the hydrophobic lipid environment on the membrane proteins (MPs) structure and function. Our work will not cover the well-studied hydrophobic mismatch between the lipid bilayer and MPs. Instead, we will focus on the less-studied direct molecular interactions of lipids with the hydrophobic surfaces of MPs.
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