Retinal dynamics underlie its switch from inverse agonist to agonist during rhodopsin activation (original) (raw)

Nature Structural & Molecular Biology volume 18, pages 392–394 (2011)Cite this article

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Abstract

X-ray and magnetic resonance approaches, though central to studies of G protein–coupled receptor (GPCR)-mediated signaling, cannot address GPCR protein dynamics or plasticity. Here we show that solid-state 2H NMR relaxation elucidates picosecond-to-nanosecond–timescale motions of the retinal ligand that influence larger-scale functional dynamics of rhodopsin in membranes. We propose a multiscale activation mechanism whereby retinal initiates collective helix fluctuations in the meta I–meta II equilibrium on the microsecond-to-millisecond timescale.

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Acknowledgements

We thank T.A. Cross, K.P. Hofmann, M. Hong, W.L. Hubbell, L.E. Kay, S.O. Smith and R.W. Pastor for discussions. Retinal was provided by K. Tanaka, S. Krane and K. Nakanishi (Columbia University). Financial support from the US National Institutes of Health (EY012049 and EY018891) is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Chemistry, University of Arizona, Tucson, Arizona, USA
    Andrey V Struts & Michael F Brown
  2. Department of Physics, St. Petersburg State University, St. Petersburg, Russia
    Andrey V Struts
  3. Département de Chimie, École Normale Supérieure, Paris, France
    Gilmar F J Salgado
  4. Torrey Pines Institute for Molecular Studies, Fort Pierce, Florida, USA
    Karina Martínez-Mayorga
  5. Department of Physics, University of Arizona, Tucson, Arizona, USA
    Michael F Brown

Authors

  1. Andrey V Struts
  2. Gilmar F J Salgado
  3. Karina Martínez-Mayorga
  4. Michael F Brown

Contributions

A.V.S. and M.F.B. designed the research. A.V.S. and G.F.J.S. performed the experiments. A.V.S., G.F.J.S., and K.M.-M. analyzed the data. A.V.S. and M.F.B. wrote the paper.

Corresponding author

Correspondence toMichael F Brown.

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The authors declare no competing financial interests.

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Struts, A., Salgado, G., Martínez-Mayorga, K. et al. Retinal dynamics underlie its switch from inverse agonist to agonist during rhodopsin activation.Nat Struct Mol Biol 18, 392–394 (2011). https://doi.org/10.1038/nsmb.1982

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