Retinal dynamics underlie its switch from inverse agonist to agonist during rhodopsin activation

Andrey V. Struts; Gilmar F.J. Salgado; Karina Martínez-Mayorga; Michael F. Brown

doi:10.1038/nsmb.1982

Retinal dynamics underlie its switch from inverse agonist to agonist during rhodopsin activation

Andrey V. Struts, Gilmar F.J. Salgado, Karina Martínez-Mayorga, Michael F. Brown

Research output: Contribution to journal › Article › peer-review

66 Scopus citations

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.

Original language	English (US)
Pages (from-to)	392-394
Number of pages	3
Journal	Nature Structural and Molecular Biology
Volume	18
Issue number	3
DOIs	https://doi.org/10.1038/nsmb.1982
State	Published - Mar 2011

ASJC Scopus subject areas

Structural Biology
Molecular Biology

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title = "Retinal dynamics underlie its switch from inverse agonist to agonist during rhodopsin activation",

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.",

author = "Struts, {Andrey V.} and Salgado, {Gilmar F.J.} and Karina Mart{\'i}nez-Mayorga and Brown, {Michael F.}",

note = "Funding Information: 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.",

year = "2011",

month = mar,

doi = "10.1038/nsmb.1982",

language = "English (US)",

volume = "18",

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AU - Struts, Andrey V.

AU - Salgado, Gilmar F.J.

AU - Martínez-Mayorga, Karina

AU - Brown, Michael F.

N1 - Funding Information: 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.

PY - 2011/3

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AB - 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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Retinal dynamics underlie its switch from inverse agonist to agonist during rhodopsin activation

Abstract

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