Author
Listed:
- Naoki Kimata
(Stony Brook University)
- Andreyah Pope
(Stony Brook University)
- Markus Eilers
(Stony Brook University)
- Chikwado A. Opefi
(School of Biological Sciences, University of Essex)
- Martine Ziliox
(Stony Brook University)
- Amiram Hirshfeld
(Weizmann Institute)
- Ekaterina Zaitseva
(University of Freiburg, Institute of Physiology II)
- Reiner Vogel
(Biophysics Section, Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University)
- Mordechai Sheves
(Weizmann Institute)
- Philip J. Reeves
(School of Biological Sciences, University of Essex)
- Steven O. Smith
(Stony Brook University)
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.
Suggested Citation
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, 2016.
"Retinal orientation and interactions in rhodopsin reveal a two-stage trigger mechanism for activation,"
Nature Communications, Nature, vol. 7(1), pages 1-10, November.
Handle:
RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12683
DOI: 10.1038/ncomms12683
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