期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2005
卷号：102
期号：18
页码：6303-6308
DOI：10.1073/pnas.0500378102
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Rhodopsins are the members of the family of G protein-coupled receptors that have diverged from ligand-binding receptors into photoreceptive pigments. Vertebrate rhodopsins are able to bind the inverse agonist 11-cis-retinal but are unable to bind the agonist all-trans-retinal, indicating that vertebrate rhodopsin changed its binding ability during the course of molecular evolution. Here, we show that unlike vertebrate rhodopsin, amphioxus rhodopsin is still able to bind the agonist all-trans-retinal. The opsin of amphioxus rhodopsin can also bind 11-cis-retinal to form a photoreceptive pigment that can convert to a red-shifted photoproduct through cis-trans isomerization of the chromophore upon photon absorption. The red-shifted photoproduct is the stable G protein activating state. Incubation of the opsin with all-trans-retinal produces a G protein activating state that is spectroscopically and biochemically indistinguishable from the red-shifted photoproduct, indicating that the opsin possesses agonist-binding ability. The opsin exhibits an {approx}50-fold higher affinity for 11-cis-retinal than for all-trans-retinal, and mutational analyses revealed that Trp-265 situated in helix VI is important for the increase in binding affinity to 11-cis-retinal. These properties of amphioxus rhodopsin suggest that an ancestral rhodopsin increased the affinity for 11-cis-retinal by rearrangement of a structure including Trp-265 to act as a photoreceptor. In addition, an additional mechanism was acquired in vertebrate rhodopsin to prevent completely the binding of exogenous all-trans-retinal during molecular evolution.
