Microbial rhodopsins are diverse photoreceptive proteins containing a retinal chromophore and are found in all domains of cellular life and are even encoded in genomes of viruses. These rhodopsins make up two families: type 1 rhodopsins and the recently discovered heliorhodopsins. These families have seven transmembrane helices with similar structures but opposing membrane orientation. Microbial rhodopsins participate in a portfolio of light-driven energy and sensory transduction processes. In this review we present data collected over the last two decades about these rhodopsins and describe their diversity, functions, and biological and ecological roles.

Schizorhodopsins, recently discovered rhodopsins in Asgard archaea, function as light-driven inward H ⁺ pumps.

Rhodopsins are photoreceptive membrane proteins consisting of a common heptahelical transmembrane architecture that contains a retinal chromophore. Rhodopsin was first discovered in the animal retina in 1876, but a different type of rhodopsin, bacteriorhodopsin, was reported to be present in the cell membrane of an extreme halophilic archaeon, Halobacterium salinarum, 95 years later. Although these findings were made by physiological observation of pigmented tissue and cell bodies, recent progress in genomic and metagenomic analyses has revealed that there are more than 10,000 microbial rhodopsins and 9000 animal rhodopsins with large diversity and tremendous new functionality. In this Cell Science at a Glance article and accompanying poster, we provide an overview of the diversity of functions, structures, color discrimination mechanisms and optogenetic applications of these two rhodopsin families, and will also highlight the third distinctive rhodopsin family, heliorhodopsin.

Microbial rhodopsins are photoreceptive membrane proteins that transport various ions using light energy. While they are widely used in optogenetics to optically control neuronal activity, rhodopsins that function with longer-wavelength light are highly demanded because of their low phototoxicity and high tissue penetration. Here, we achieve a 40-nm red-shift in the absorption wavelength of a sodium-pump rhodopsin (KR2) by altering dipole moment of residues around the retinal chromophore (KR2 P219T/S254A) without impairing its ion-transport activity. Structural differences in the chromophore of the red-shifted protein from that of the wildtype are observed by Fourier transform infrared spectroscopy. QM/MM models generated with an automated protocol show that the changes in the electrostatic interaction between protein and chromophore induced by the amino-acid replacements, lowered the energy gap between the ground and the first electronically excited state. Based on these insights, a natural sodium pump with red-shifted absorption is identified from Jannaschia seosinensis.

Channelrhodopsins (ChRs) are microbial light-gated ion channels utilized in optogenetics to control neural activity with light . Light absorption causes retinal chromophore isomerization and subsequent protein conformational changes visualized as optically distinguished intermediates, coupled with channel opening and closing. However, the detailed molecular events underlying channel gating remain unknown. We performed time-resolved serial femtosecond crystallographic analyses of ChR by using an X-ray free electron laser, which revealed conformational changes following photoactivation. The isomerized retinal adopts a twisted conformation and shifts toward the putative internal proton donor residues, consequently inducing an outward shift of TM3, as well as a local deformation in TM7. These early conformational changes in the pore-forming helices should be the triggers that lead to opening of the ion conducting pore.