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An all-trans-retinal-binding opsin peropsin as a potential dark-active and light-inactivated G protein-coupled receptor

Peropsin or retinal pigment epithelium-derived rhodopsin homolog, found in many animals, belongs to the opsin family. Most opsins bind to 11-cis-retinal as a chromophore and act as light-activated G protein-coupled receptors. Some peropsins, however, bind all-trans-retinal and isomerise it into 11-c...

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Autores principales: Nagata, Takashi, Koyanagi, Mitsumasa, Lucas, Robert, Terakita, Akihisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824942/
https://www.ncbi.nlm.nih.gov/pubmed/29476064
http://dx.doi.org/10.1038/s41598-018-21946-1
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author Nagata, Takashi
Koyanagi, Mitsumasa
Lucas, Robert
Terakita, Akihisa
author_facet Nagata, Takashi
Koyanagi, Mitsumasa
Lucas, Robert
Terakita, Akihisa
author_sort Nagata, Takashi
collection PubMed
description Peropsin or retinal pigment epithelium-derived rhodopsin homolog, found in many animals, belongs to the opsin family. Most opsins bind to 11-cis-retinal as a chromophore and act as light-activated G protein-coupled receptors. Some peropsins, however, bind all-trans-retinal and isomerise it into 11-cis form by light, and peropsin has been suggested to supply other visual opsins with 11-cis-retinal. Additionally, peropsin has some amino acid sequence motifs that are highly conserved among G protein-coupled opsins. Here, using chimeric mutant peropsins, we found that peropsin potentially generates an “active form” that drives G-protein signalling in the dark by binding to all-trans-retinal and that the active form photo-converts to an inactive form containing 11-cis-retinal. Comparative spectroscopic analysis demonstrated that spider peropsin exhibited catalytic efficiency for retinal photoisomerisation that was much lower than a retinal photoisomerase, squid retinochrome. The chimeric peropsins, constructed by replacing the third intracellular loop region with that of Gs- or Gi-coupled opsin, were active and drove Gs- or Gi-mediated signalling in the dark, respectively, and were inactivated upon illumination in mammalian cultured cells. These results suggest that peropsin acts as a dark-active, light-inactivated G protein-coupled receptor and is useful as a novel optogenetic tool.
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spelling pubmed-58249422018-03-01 An all-trans-retinal-binding opsin peropsin as a potential dark-active and light-inactivated G protein-coupled receptor Nagata, Takashi Koyanagi, Mitsumasa Lucas, Robert Terakita, Akihisa Sci Rep Article Peropsin or retinal pigment epithelium-derived rhodopsin homolog, found in many animals, belongs to the opsin family. Most opsins bind to 11-cis-retinal as a chromophore and act as light-activated G protein-coupled receptors. Some peropsins, however, bind all-trans-retinal and isomerise it into 11-cis form by light, and peropsin has been suggested to supply other visual opsins with 11-cis-retinal. Additionally, peropsin has some amino acid sequence motifs that are highly conserved among G protein-coupled opsins. Here, using chimeric mutant peropsins, we found that peropsin potentially generates an “active form” that drives G-protein signalling in the dark by binding to all-trans-retinal and that the active form photo-converts to an inactive form containing 11-cis-retinal. Comparative spectroscopic analysis demonstrated that spider peropsin exhibited catalytic efficiency for retinal photoisomerisation that was much lower than a retinal photoisomerase, squid retinochrome. The chimeric peropsins, constructed by replacing the third intracellular loop region with that of Gs- or Gi-coupled opsin, were active and drove Gs- or Gi-mediated signalling in the dark, respectively, and were inactivated upon illumination in mammalian cultured cells. These results suggest that peropsin acts as a dark-active, light-inactivated G protein-coupled receptor and is useful as a novel optogenetic tool. Nature Publishing Group UK 2018-02-23 /pmc/articles/PMC5824942/ /pubmed/29476064 http://dx.doi.org/10.1038/s41598-018-21946-1 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Nagata, Takashi
Koyanagi, Mitsumasa
Lucas, Robert
Terakita, Akihisa
An all-trans-retinal-binding opsin peropsin as a potential dark-active and light-inactivated G protein-coupled receptor
title An all-trans-retinal-binding opsin peropsin as a potential dark-active and light-inactivated G protein-coupled receptor
title_full An all-trans-retinal-binding opsin peropsin as a potential dark-active and light-inactivated G protein-coupled receptor
title_fullStr An all-trans-retinal-binding opsin peropsin as a potential dark-active and light-inactivated G protein-coupled receptor
title_full_unstemmed An all-trans-retinal-binding opsin peropsin as a potential dark-active and light-inactivated G protein-coupled receptor
title_short An all-trans-retinal-binding opsin peropsin as a potential dark-active and light-inactivated G protein-coupled receptor
title_sort all-trans-retinal-binding opsin peropsin as a potential dark-active and light-inactivated g protein-coupled receptor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824942/
https://www.ncbi.nlm.nih.gov/pubmed/29476064
http://dx.doi.org/10.1038/s41598-018-21946-1
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