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

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.

Abstract

Rhodopsin signalling is triggered by the light-induced isomerization of its 11- cis retinal chromophore. Here, the authors use NMR spectroscopy to define retinal orientation and interactions in the active metarhodopsin II intermediate, proposing a two-stage mechanism for rhodopsin activation.