Abstract
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.
Funder
NCCR Molecular Systems Engineering
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
X-Probe ITN
Peter und Traudl Engelhorn Stiftung
European Community's Seventh Framework Program/COFUND PSI fellow
SNI-Nanoargovia
Japanese Ministry of Education, Culture, Sports, Science and Technology Grants-in-Aid for Scientific Research
Technology Agency (JST) Core Research for Evolutional Science and Technology
Publisher
Proceedings of the National Academy of Sciences
Cited by
47 articles.
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