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Light-sensitive G protein-coupled receptors (GPCRs)-rhodopsins-absorb photons to isomerize their covalently bound retinal, triggering conformational changes that result in downstream signaling cascades. Monostable rhodopsins release retinal upon isomerization as opposed to the retinal in bistable rhodopsins that "reisomerize" upon absorption of a second photon. Understanding the mechanistic differences between these light-sensitive GPCRs has been hindered by the scarcity of recombinant models of the latter. Here, we reveal the high-resolution crystal structure of a recombinant bistable rhodopsin, jumping spider rhodopsin-1, bound to the inverse agonist 9-cis retinal. We observe a water-mediated network around the ligand hinting toward the basis of their bistable nature. In contrast to bovine rhodopsin (monostable), the transmembrane bundle of jumping spider rhodopsin-1 as well that of the bistable squid rhodopsin adopts a more "activation-ready" conformation often observed in other nonphotosensitive class A GPCRs. These similarities suggest the role of jumping spider rhodopsin-1 as a potential model system in the study of the structure-function relationship of both photosensitive and nonphotosensitive class A GPCRs., Proceedings of the National Academy of Sciences of the United States of America, 116 (29), ISSN:0027-8424, ISSN:1091-6490

Photoreception and light transformation by living systems undoubtedly belong to the most surprising natural phenomena. Along with low-M, chromophoric compounds, specific proteins play an important part in absorption and transduction of light energy. Among photosensitive proteins, rhodopsin occupies a key position. This chromoprotein, with 1 l-c&retinal as a photoreceptor antenna, is the basis of the vision process in animals. For a long time all attempts to isolate rhodopsin from the photosensitive disc membranes in an individual and active state were not a success. The preparations obtained with various detergents were unsuitable for detailed structural analysis. Though dozens of laboratories actively participated in investigations of rhodopsin function and its structure peculiarities [l-6], the progress was rather slow. gradient of H+ turned out to be a universal energetic source for the cell. Interestingly, full protonpumping activity has been restored after complete delipidation and following reconstitution of bacteriorhodopsin into liposomes [ 16-l 81.