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Crystal structure of jumping spider rhodopsin-1 as a light sensitive GPCR

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 rh...

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Autores principales: Varma, Niranjan, Mutt, Eshita, Mühle, Jonas, Panneels, Valérie, Terakita, Akihisa, Deupi, Xavier, Nogly, Przemyslaw, Schertler, Gebhard F. X., Lesca, Elena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642406/
https://www.ncbi.nlm.nih.gov/pubmed/31249143
http://dx.doi.org/10.1073/pnas.1902192116
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author Varma, Niranjan
Mutt, Eshita
Mühle, Jonas
Panneels, Valérie
Terakita, Akihisa
Deupi, Xavier
Nogly, Przemyslaw
Schertler, Gebhard F. X.
Lesca, Elena
author_facet Varma, Niranjan
Mutt, Eshita
Mühle, Jonas
Panneels, Valérie
Terakita, Akihisa
Deupi, Xavier
Nogly, Przemyslaw
Schertler, Gebhard F. X.
Lesca, Elena
author_sort Varma, Niranjan
collection PubMed
description 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.
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spelling pubmed-66424062019-07-25 Crystal structure of jumping spider rhodopsin-1 as a light sensitive GPCR Varma, Niranjan Mutt, Eshita Mühle, Jonas Panneels, Valérie Terakita, Akihisa Deupi, Xavier Nogly, Przemyslaw Schertler, Gebhard F. X. Lesca, Elena Proc Natl Acad Sci U S A PNAS Plus 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. National Academy of Sciences 2019-07-16 2019-06-28 /pmc/articles/PMC6642406/ /pubmed/31249143 http://dx.doi.org/10.1073/pnas.1902192116 Text en Copyright © 2019 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle PNAS Plus
Varma, Niranjan
Mutt, Eshita
Mühle, Jonas
Panneels, Valérie
Terakita, Akihisa
Deupi, Xavier
Nogly, Przemyslaw
Schertler, Gebhard F. X.
Lesca, Elena
Crystal structure of jumping spider rhodopsin-1 as a light sensitive GPCR
title Crystal structure of jumping spider rhodopsin-1 as a light sensitive GPCR
title_full Crystal structure of jumping spider rhodopsin-1 as a light sensitive GPCR
title_fullStr Crystal structure of jumping spider rhodopsin-1 as a light sensitive GPCR
title_full_unstemmed Crystal structure of jumping spider rhodopsin-1 as a light sensitive GPCR
title_short Crystal structure of jumping spider rhodopsin-1 as a light sensitive GPCR
title_sort crystal structure of jumping spider rhodopsin-1 as a light sensitive gpcr
topic PNAS Plus
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642406/
https://www.ncbi.nlm.nih.gov/pubmed/31249143
http://dx.doi.org/10.1073/pnas.1902192116
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