Research Highlights
Andreyah Pope (4th Year Student)
Retinal orientation and interactions in rhodopsin reveal a two stage trigger mechanism for activation . Nature Communications 7, 12683
The 11-
cis retinal chromophore of the visual receptor rhodopsin is tightly packed within the
protein’s in
terior. Solid-state NMR spectroscopy is used to define the orientation and interactions
of the retinal chromophore in the active Metarhodopsin II intermediate trapped along
its photoreaction pathway. The orientation of the retinal differs from that in recent
active-state rhodopsin crystal structures. We show that retinal isomerization generates
strong steric interactions with transmembrane helices H5 and H6 via contacts with
the ionone portion of the retinal, while deprotonation of the retinal Schiff base
triggers the rearrangement of hydrogen-bonding interactions involving residues on
helix 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 to describe how absorbed light energy is channeled into the protein
to direct the known outward rotation of transmembrane helix H6, a hallmark of active
G protein-coupled receptors.
