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

Kimata, N and Pope, A and Eilers, M and Opefi, CA and Ziliox, M and Hirshfeld, A and Zaitseva, E and Vogel, R and Sheves, M and Reeves, PJ and Smith, SO (2016) 'Retinal orientation and interactions in rhodopsin reveal a two-stage trigger mechanism for activation.' Nature Communications, 7. ISSN 2041-1723

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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
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science and Health > Life Sciences, School of
Depositing User: Philip Reeves
Date Deposited: 18 Oct 2016 12:17
Last Modified: 07 Apr 2021 10:16

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