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 journalArticlepeer-review

34 Citations (Scopus)


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 languageEnglish
Article number12683
JournalNature communications
Publication statusPublished - 2016 Sept 2
Externally publishedYes

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General
  • General Physics and Astronomy


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