Kimata, Naoki and Pope, Andreyah and Eilers, Markus and Opefi, Chikwado A and Ziliox, Martine and Hirshfeld, Amiram and Zaitseva, Ekaterina and Vogel, Reiner and Sheves, Mordechai and Reeves, Philip J and Smith, Steven O (2016) Retinal orientation and interactions in rhodopsin reveal a two-stage trigger mechanism for activation. Nature Communications, 7 (1). 12683-. DOI https://doi.org/10.1038/ncomms12683
Kimata, Naoki and Pope, Andreyah and Eilers, Markus and Opefi, Chikwado A and Ziliox, Martine and Hirshfeld, Amiram and Zaitseva, Ekaterina and Vogel, Reiner and Sheves, Mordechai and Reeves, Philip J and Smith, Steven O (2016) Retinal orientation and interactions in rhodopsin reveal a two-stage trigger mechanism for activation. Nature Communications, 7 (1). 12683-. DOI https://doi.org/10.1038/ncomms12683
Kimata, Naoki and Pope, Andreyah and Eilers, Markus and Opefi, Chikwado A and Ziliox, Martine and Hirshfeld, Amiram and Zaitseva, Ekaterina and Vogel, Reiner and Sheves, Mordechai and Reeves, Philip J and Smith, Steven O (2016) Retinal orientation and interactions in rhodopsin reveal a two-stage trigger mechanism for activation. Nature Communications, 7 (1). 12683-. DOI https://doi.org/10.1038/ncomms12683
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.
Item Type: | Article |
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Uncontrolled Keywords: | Retina; Cell Line; Humans; Retinaldehyde; Rhodopsin; Spectroscopy, Fourier Transform Infrared; Nuclear Magnetic Resonance, Biomolecular; Protein Structure, Tertiary; Models, Molecular; HEK293 Cells |
Subjects: | Q Science > QH Natural history > QH301 Biology |
Divisions: | Faculty of Science and Health Faculty of Science and Health > Life Sciences, School of |
SWORD Depositor: | Unnamed user with email elements@essex.ac.uk |
Depositing User: | Unnamed user with email elements@essex.ac.uk |
Date Deposited: | 18 Oct 2016 12:17 |
Last Modified: | 30 Oct 2024 20:12 |
URI: | http://repository.essex.ac.uk/id/eprint/17646 |
Available files
Filename: ncomms12683 (1).pdf
Licence: Creative Commons: Attribution 3.0