Retinal orientation and interactions in rhodopsin reveal a two-stage trigger mechanism for activation

Naoki Kimata; Andreyah Pope; Markus Eilers; Chikwado A. Opefi; Martine Ziliox; Amiram Hirshfeld; Ekaterina Zaitseva; Reiner Vogel; Mordechai Sheves; Philip J. Reeves; Steven O. Smith

doi:10.1038/ncomms12683

Retinal orientation and interactions in rhodopsin reveal a two-stage trigger mechanism for activation

Naoki Kimata, Andreyah Pope, Markus Eilers, Chikwado A. Opefi, Martine Ziliox, Amiram Hirshfeld, Ekaterina Zaitseva, Reiner Vogel, Mordechai Sheves, Philip J. Reeves, Steven O. Smith^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

29 Citations (Scopus)

Abstract

The 11-cis retinal chromophore is tightly packed within the interior of the visual receptor rhodopsin and isomerizes to the all-trans configuration following absorption of light. The mechanism by which this isomerization event drives the outward rotation of transmembrane helix H6, a hallmark of activated G protein-coupled receptors, is not well established. To address this question, we use solid-state NMR and FTIR spectroscopy to define the orientation and interactions of the retinal chromophore in the active metarhodopsin II intermediate. Here we show that isomerization of the 11-cis retinal chromophore generates strong steric interactions between its β-ionone ring and transmembrane helices H5 and H6, while deprotonation of its protonated Schiff's base triggers the rearrangement of the hydrogen-bonding network involving residues on H6 and within the second extracellular loop. We integrate these observations with previous structural and functional studies to propose a two-stage mechanism for rhodopsin activation.

Original language	English
Article number	12683
Journal	Nature communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms12683
Publication status	Published - 2016 Sept 2
Externally published	Yes

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
General
Physics and Astronomy(all)

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@article{a2925accfd0b49efb512bae112694e75,

title = "Retinal orientation and interactions in rhodopsin reveal a two-stage trigger mechanism for activation",

abstract = "The 11-cis retinal chromophore is tightly packed within the interior of the visual receptor rhodopsin and isomerizes to the all-trans configuration following absorption of light. The mechanism by which this isomerization event drives the outward rotation of transmembrane helix H6, a hallmark of activated G protein-coupled receptors, is not well established. To address this question, we use solid-state NMR and FTIR spectroscopy to define the orientation and interactions of the retinal chromophore in the active metarhodopsin II intermediate. Here we show that isomerization of the 11-cis retinal chromophore generates strong steric interactions between its β-ionone ring and transmembrane helices H5 and H6, while deprotonation of its protonated Schiff's base triggers the rearrangement of the hydrogen-bonding network involving residues on H6 and within the second extracellular loop. We integrate these observations with previous structural and functional studies to propose a two-stage mechanism for rhodopsin activation.",

author = "Naoki Kimata and Andreyah Pope and Markus Eilers and Opefi, {Chikwado A.} and Martine Ziliox and Amiram Hirshfeld and Ekaterina Zaitseva and Reiner Vogel and Mordechai Sheves and Reeves, {Philip J.} and Smith, {Steven O.}",

note = "Funding Information: This work was supported by a grant from the NIH (GM 41412) to S.O.S. Publisher Copyright: {\textcopyright} 2016 The Author(s).",

year = "2016",

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doi = "10.1038/ncomms12683",

language = "English",

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AU - Kimata, Naoki

AU - Pope, Andreyah

AU - Eilers, Markus

AU - Opefi, Chikwado A.

AU - Ziliox, Martine

AU - Hirshfeld, Amiram

AU - Zaitseva, Ekaterina

AU - Vogel, Reiner

AU - Sheves, Mordechai

AU - Reeves, Philip J.

AU - Smith, Steven O.

PY - 2016/9/2

Y1 - 2016/9/2

N2 - The 11-cis retinal chromophore is tightly packed within the interior of the visual receptor rhodopsin and isomerizes to the all-trans configuration following absorption of light. The mechanism by which this isomerization event drives the outward rotation of transmembrane helix H6, a hallmark of activated G protein-coupled receptors, is not well established. To address this question, we use solid-state NMR and FTIR spectroscopy to define the orientation and interactions of the retinal chromophore in the active metarhodopsin II intermediate. Here we show that isomerization of the 11-cis retinal chromophore generates strong steric interactions between its β-ionone ring and transmembrane helices H5 and H6, while deprotonation of its protonated Schiff's base triggers the rearrangement of the hydrogen-bonding network involving residues on H6 and within the second extracellular loop. We integrate these observations with previous structural and functional studies to propose a two-stage mechanism for rhodopsin activation.

AB - The 11-cis retinal chromophore is tightly packed within the interior of the visual receptor rhodopsin and isomerizes to the all-trans configuration following absorption of light. The mechanism by which this isomerization event drives the outward rotation of transmembrane helix H6, a hallmark of activated G protein-coupled receptors, is not well established. To address this question, we use solid-state NMR and FTIR spectroscopy to define the orientation and interactions of the retinal chromophore in the active metarhodopsin II intermediate. Here we show that isomerization of the 11-cis retinal chromophore generates strong steric interactions between its β-ionone ring and transmembrane helices H5 and H6, while deprotonation of its protonated Schiff's base triggers the rearrangement of the hydrogen-bonding network involving residues on H6 and within the second extracellular loop. We integrate these observations with previous structural and functional studies to propose a two-stage mechanism for rhodopsin activation.

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Retinal orientation and interactions in rhodopsin reveal a two-stage trigger mechanism for activation

Abstract

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