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Helix Movement is Coupled to Displacement of the Second Extracellular Loop in Rhodopsin Activation

The second extracellular loop (EL2) of rhodopsin forms a cap over the binding site of its photoreactive 11-cis retinylidene chromophore. A critical question has been whether EL2 forms a reversible gate that opens upon activation or acts as a rigid barrier. Distance measurements using solid-state (13...

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Autores principales: Ahuja, Shivani, Hornak, Viktor, Yan, Elsa C. Y., Syrett, Natalie, Goncalves, Joseph A., Hirshfeld, Amiram, Ziliox, Martine, Sakmar, Thomas P., Sheves, Mordechai, Reeves, Philip J., Smith, Steven O., Eilers, Markus
Formato: Texto
Lenguaje:English
Publicado: 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2705779/
https://www.ncbi.nlm.nih.gov/pubmed/19182802
http://dx.doi.org/10.1038/nsmb.1549
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author Ahuja, Shivani
Hornak, Viktor
Yan, Elsa C. Y.
Syrett, Natalie
Goncalves, Joseph A.
Hirshfeld, Amiram
Ziliox, Martine
Sakmar, Thomas P.
Sheves, Mordechai
Reeves, Philip J.
Smith, Steven O.
Eilers, Markus
author_facet Ahuja, Shivani
Hornak, Viktor
Yan, Elsa C. Y.
Syrett, Natalie
Goncalves, Joseph A.
Hirshfeld, Amiram
Ziliox, Martine
Sakmar, Thomas P.
Sheves, Mordechai
Reeves, Philip J.
Smith, Steven O.
Eilers, Markus
author_sort Ahuja, Shivani
collection PubMed
description The second extracellular loop (EL2) of rhodopsin forms a cap over the binding site of its photoreactive 11-cis retinylidene chromophore. A critical question has been whether EL2 forms a reversible gate that opens upon activation or acts as a rigid barrier. Distance measurements using solid-state (13)C NMR spectroscopy between the retinal chromophore and the β4 strand of EL2 show the loop is displaced from the retinal binding site upon activation, and there is a rearrangement in the hydrogen-bonding networks connecting EL2 with the extracellular ends of transmembrane helices H4, H5 and H6. NMR measurements further reveal that structural changes in EL2 are coupled to the motion of helix H5 and breaking of the ionic lock that regulates activation. These results provide a comprehensive view of how retinal isomerization triggers helix motion and activation in this prototypical G protein-coupled receptor.
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spelling pubmed-27057792009-08-01 Helix Movement is Coupled to Displacement of the Second Extracellular Loop in Rhodopsin Activation Ahuja, Shivani Hornak, Viktor Yan, Elsa C. Y. Syrett, Natalie Goncalves, Joseph A. Hirshfeld, Amiram Ziliox, Martine Sakmar, Thomas P. Sheves, Mordechai Reeves, Philip J. Smith, Steven O. Eilers, Markus Nat Struct Mol Biol Article The second extracellular loop (EL2) of rhodopsin forms a cap over the binding site of its photoreactive 11-cis retinylidene chromophore. A critical question has been whether EL2 forms a reversible gate that opens upon activation or acts as a rigid barrier. Distance measurements using solid-state (13)C NMR spectroscopy between the retinal chromophore and the β4 strand of EL2 show the loop is displaced from the retinal binding site upon activation, and there is a rearrangement in the hydrogen-bonding networks connecting EL2 with the extracellular ends of transmembrane helices H4, H5 and H6. NMR measurements further reveal that structural changes in EL2 are coupled to the motion of helix H5 and breaking of the ionic lock that regulates activation. These results provide a comprehensive view of how retinal isomerization triggers helix motion and activation in this prototypical G protein-coupled receptor. 2009-02-01 2009-02 /pmc/articles/PMC2705779/ /pubmed/19182802 http://dx.doi.org/10.1038/nsmb.1549 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Ahuja, Shivani
Hornak, Viktor
Yan, Elsa C. Y.
Syrett, Natalie
Goncalves, Joseph A.
Hirshfeld, Amiram
Ziliox, Martine
Sakmar, Thomas P.
Sheves, Mordechai
Reeves, Philip J.
Smith, Steven O.
Eilers, Markus
Helix Movement is Coupled to Displacement of the Second Extracellular Loop in Rhodopsin Activation
title Helix Movement is Coupled to Displacement of the Second Extracellular Loop in Rhodopsin Activation
title_full Helix Movement is Coupled to Displacement of the Second Extracellular Loop in Rhodopsin Activation
title_fullStr Helix Movement is Coupled to Displacement of the Second Extracellular Loop in Rhodopsin Activation
title_full_unstemmed Helix Movement is Coupled to Displacement of the Second Extracellular Loop in Rhodopsin Activation
title_short Helix Movement is Coupled to Displacement of the Second Extracellular Loop in Rhodopsin Activation
title_sort helix movement is coupled to displacement of the second extracellular loop in rhodopsin activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2705779/
https://www.ncbi.nlm.nih.gov/pubmed/19182802
http://dx.doi.org/10.1038/nsmb.1549
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