Solid-state 2H NMR relaxation illuminates functional dynamics of retinal cofactor in membrane activation of rhodopsin

Andrey V. Struts, Gilmar F.J. Salgado, Michael F. Brown

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


Rhodopsin is a canonical member of the family of G protein-coupled receptors, which transmit signals across cellular membranes and are linked to many drug interventions in humans. Here we show that solid-state 2H NMR relaxation allows investigation of light-induced changes in local ps-ns time scale motions of retinal bound to rhodopsin. Site-specific 2H labels were introduced into methyl groups of the retinal ligand that are essential to the activation process. We conducted solid-state 2H NMR relaxation (spin-lattice, T1Z, and quadrupolar-order, T1Q) experiments in the dark, Meta I, and Meta II states of the photoreceptor. Surprisingly, we find the retinylidene methyl groups exhibit site-specific differences in dynamics that change upon light excitation - even more striking, the C9-methyl group is a dynamical hotspot that corresponds to a crucial functional hotspot of rhodopsin. Following 11-cis to trans isomerization, the 2H NMR data suggest the β-ionone ring remains in its hydrophobic binding pocket in all three states of the protein. We propose a multiscale activation mechanism with a complex energy landscape, whereby the photonic energy is directed against the E2 loop by the C13-methyl group, and toward helices H3 and H5 by the C5-methyl of the β-ionone ring. Changes in retinal structure and dynamics initiate activating fluctuations of transmembrane helices H5 and H6 in the Meta I-Meta II equilibrium of rhodopsin. Our proposals challenge the Standard Model whereby a single light-activated receptor conformation yields the visual response - rather an ensemble of substates is present, due to the entropy gain produced by photolysis of the inhibitory retinal lock.

Original languageEnglish (US)
Pages (from-to)8263-8268
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number20
StatePublished - May 17 2011


  • GPCR
  • Generalized model-free analysis
  • Solid-state NMR

ASJC Scopus subject areas

  • General


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