| Solid-state 2H NMR relaxation illuminates functional dynamics of retinal cofactor in membrane activation of rhodopsin. | |
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MedLine Citation:
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PMID: 21527723 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 (2)H NMR relaxation allows investigation of light-induced changes in local ps-ns time scale motions of retinal bound to rhodopsin. Site-specific (2)H labels were introduced into methyl groups of the retinal ligand that are essential to the activation process. We conducted solid-state (2)H NMR relaxation (spin-lattice, T(1Z), and quadrupolar-order, T(1Q)) 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 (2)H 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. |
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Authors:
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Andrey V Struts; Gilmar F J Salgado; Michael F Brown |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-04-28 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 108 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-05-18 Completed Date: 2011-07-26 Revised Date: 2011-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 8263-8 Citation Subset: IM |
Affiliation:
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Department of Chemistry, University of Arizona, Tucson, AZ 85721, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cattle Cell Membrane Light* Magnetic Resonance Spectroscopy* Membrane Proteins Protein Conformation Retinaldehyde / radiation effects* Rhodopsin / chemistry*, metabolism Thermodynamics |
| Chemical | |
Reg. No./Substance:
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0/Membrane Proteins; 116-31-4/Retinaldehyde; 9009-81-8/Rhodopsin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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