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

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-. 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
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: Elements
Depositing User: Elements
Date Deposited: 18 Oct 2016 12:17
Last Modified: 06 Jan 2022 14:40

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