{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:17:29Z","timestamp":1791825449919,"version":"4.3.4"},"reference-count":50,"publisher":"National Academy of Sciences","issue":"20","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,5,17]]},"abstract":"<jats:p>\n                    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\n                    <jats:sup>2<\/jats:sup>\n                    H NMR relaxation allows investigation of light-induced changes in local ps\u2013ns time scale motions of retinal bound to rhodopsin. Site-specific\n                    <jats:sup>2<\/jats:sup>\n                    H labels were introduced into methyl groups of the retinal ligand that are essential to the activation process. We conducted solid-state\n                    <jats:sup>2<\/jats:sup>\n                    H NMR relaxation (spin-lattice,\n                    <jats:italic>T<\/jats:italic>\n                    <jats:sub>\n                      1\n                      <jats:italic>Z<\/jats:italic>\n                    <\/jats:sub>\n                    , and quadrupolar-order,\n                    <jats:italic>T<\/jats:italic>\n                    <jats:sub>\n                      1\n                      <jats:italic>Q<\/jats:italic>\n                    <\/jats:sub>\n                    ) 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\u2014even more striking, the C9-methyl group is a dynamical hotspot that corresponds to a crucial functional hotspot of rhodopsin. Following 11-\n                    <jats:italic>cis<\/jats:italic>\n                    to\n                    <jats:italic>trans<\/jats:italic>\n                    isomerization, the\n                    <jats:sup>2<\/jats:sup>\n                    H NMR data suggest the\n                    <jats:italic>\u03b2<\/jats:italic>\n                    -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\n                    <jats:italic>\u03b2<\/jats:italic>\n                    -ionone ring. Changes in retinal structure and dynamics initiate activating fluctuations of transmembrane helices H5 and H6 in the Meta I\u2013Meta II equilibrium of rhodopsin. Our proposals challenge the Standard Model whereby a single light-activated receptor conformation yields the visual response\u2014rather an ensemble of substates is present, due to the entropy gain produced by photolysis of the inhibitory retinal lock.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1014692108","type":"journal-article","created":{"date-parts":[[2011,4,28]],"date-time":"2011-04-28T21:07:22Z","timestamp":1304024842000},"page":"8263-8268","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":53,"title":["Solid-state\n                    <sup>2<\/sup>\n                    H NMR relaxation illuminates functional dynamics of retinal cofactor in membrane activation of rhodopsin"],"prefix":"10.1073","volume":"108","author":[{"given":"Andrey V.","family":"Struts","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Arizona, Tucson, AZ 85721;"},{"name":"Department of Physics, St. Petersburg State University, St. Petersburg 198904, Russia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilmar F. J.","family":"Salgado","sequence":"additional","affiliation":[{"name":"Laboratoire ARNA, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U869, Institut Europ\u00e9en de Chemie et Biologie (IECB), Universit\u00e9 de Bordeaux, F-33000 Bordeaux, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael F.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Arizona, Tucson, AZ 85721;"},{"name":"Department of Physics, University of Arizona, Tucson, AZ 85721"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,4,28]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.48.1399"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08144"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2009.02.006"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5480.739"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2004.07.044"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2004.08.090"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2007.03.007"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06925"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09648"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09746"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1164772"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600374"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601765103"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0608022103"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(00)15842-2"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1118379"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0804541105"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M805725200"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07063"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07330"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0009-3084(94)90180-5"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.106.082776"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0802515105"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.112677599"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2004.08.049"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1549"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja910317a"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biophys.050708.133719"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1982"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.443940"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevE.58.2259"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi0491191"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi0508587"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi052196r"},{"key":"e_1_3_3_35_2","first-page":"107","article-title":"Spin-lattice relaxation in solids","volume":"49","author":"Torchia DA","year":"1982","unstructured":"DA Torchia, A Szabo, Spin-lattice relaxation in solids. 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