{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T09:50:32Z","timestamp":1792057832791,"version":"4.4.0"},"reference-count":58,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["Equipe DEQ20170336747 to JPP"],"award-info":[{"award-number":["Equipe DEQ20170336747 to JPP"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>G protein\u2010coupled receptors (GPCRs) constitute the largest family of drug targets, acting through heterotrimeric G proteins. Agonist bound GPCRs promote GDP release from G proteins allowing their activation upon GTP binding. Here, we analyze this process with innovative tools that detect the main states of native Gi proteins: the GDP\u2010bound, the open nucleotide\u2010free and the active GTP\u2010bound states. We show that receptor activation increases the amount of open\u2010state Gi proteins, consistent with GDP release from inactive Gi proteins. We also observe that the active receptor can release GTP from the active Gi protein, to return to an inactive open state. Consistently, receptor activation also promotes the formation of the G\u03b1\u03b2\u03b3 complex from the GTP\u2010bound state in cells, in agreement with the formation of the receptor\u2010G protein ternary complex. These data suggest that the amount of active GTP\u2010bound form produced upon GPCR activation can be controlled by the receptor\u2010induced GTP release. This control of G protein state equilibrium that depends on the receptor subtype may affect coupling efficacy. These data reveal receptor\u2010dependent G\u2010protein state equilibria and identify GTP release as an additional, context\u2010dependent control point that can shape apparent coupling efficacy.<\/jats:p>","DOI":"10.1002\/advs.77969","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T09:40:31Z","timestamp":1792057231000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Innovative Approach Reveals How Receptors Control G Protein State Equilibria"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9294-2229","authenticated-orcid":false,"given":"Alexandre","family":"Bouyssou","sequence":"first","affiliation":[{"name":"CNRS Institut De G\u00e9nomique Fonctionnelle (IGF) Inserm Universit\u00e9 De Montpellier  Montpellier France"},{"name":"Revvity  Codolet France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Da Silva","sequence":"additional","affiliation":[{"name":"CNRS Institut De G\u00e9nomique Fonctionnelle (IGF) Inserm Universit\u00e9 De Montpellier  Montpellier France"},{"name":"Revvity  Codolet France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Soul\u00e9","sequence":"additional","affiliation":[{"name":"CNRS Institut De G\u00e9nomique Fonctionnelle (IGF) Inserm Universit\u00e9 De Montpellier  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovic","family":"Fabre","sequence":"additional","affiliation":[{"name":"CNRS Institut De G\u00e9nomique Fonctionnelle (IGF) Inserm Universit\u00e9 De Montpellier  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Lamarque","sequence":"additional","affiliation":[{"name":"Revvity  Codolet France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7802-2838","authenticated-orcid":false,"given":"R\u00e9my","family":"Sounier","sequence":"additional","affiliation":[{"name":"CNRS Institut De G\u00e9nomique Fonctionnelle (IGF) Inserm Universit\u00e9 De Montpellier  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Durroux","sequence":"additional","affiliation":[{"name":"CNRS Institut De G\u00e9nomique Fonctionnelle (IGF) Inserm Universit\u00e9 De Montpellier  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Granier","sequence":"additional","affiliation":[{"name":"CNRS Institut De G\u00e9nomique Fonctionnelle (IGF) Inserm Universit\u00e9 De Montpellier  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6453-7642","authenticated-orcid":false,"given":"Thomas","family":"Roux","sequence":"additional","affiliation":[{"name":"Revvity  Codolet France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Dupuis","sequence":"additional","affiliation":[{"name":"Revvity  Codolet France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Trinquet","sequence":"additional","affiliation":[{"name":"Revvity  Codolet France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1134-2738","authenticated-orcid":false,"given":"Philippe","family":"Rondard","sequence":"additional","affiliation":[{"name":"CNRS Institut De G\u00e9nomique Fonctionnelle (IGF) Inserm Universit\u00e9 De Montpellier  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1423-345X","authenticated-orcid":false,"given":"Jean\u2010Philippe","family":"Pin","sequence":"additional","affiliation":[{"name":"CNRS Institut De G\u00e9nomique Fonctionnelle (IGF) Inserm Universit\u00e9 De Montpellier  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2017.178"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2017.229"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa5264"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba3373"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1604125113"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010022\u201005343\u20103"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.08.052"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10361"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0811437106"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2002665117"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010018\u20100219\u20107"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00928361"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021\u20109258(18)89245\u20106"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006\u20103495(87)83214\u20109"},{"issue":"10","key":"e_1_2_9_16_1","first-page":"2662","article-title":"Biochemical Mechanisms of Hormone Receptor\u2010Effector Coupling. Introduction","volume":"41","author":"Lefkowitz R. J.","year":"1982","journal-title":"Federation Proceedings"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0042\u20106989(82)90212\u20107"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432\u20101033.1992.tb16687.x"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0898\u20106568(93)90082\u2010w"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201066516\u2010y"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010025\u201009880\u20105"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.74101"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.74107"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.04.044"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1905993116"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15811"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0165\u20106147(02)00027\u20105"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476\u20105381.2010.00963.x"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2536719100"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb1134"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.06.020"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589\u2010020\u20100535\u20108"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aab4068"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2009.10.028"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1089\/adt.2005.3.637"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1006\/abio.2001.5011"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471\u20104159.2007.05131.x"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.2174\/138620708784534798"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.11.132"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2014.06.003"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1113645108"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2006.04.042"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589\u2010022\u201001050\u20102"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi0613832"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102164\u201012\u201014"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2021.07.004"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707941200"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth743"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702816"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2009.02.078"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022\u20103565(24)36877\u20106"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.476234"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2015.07.001"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/0922\u20104106(93)90064\u2010g"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.56.070187.003151"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021\u20109258(18)33483\u20105"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.015388"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.125re5"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201036911\u20104"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77969","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.77969","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77969","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T09:40:32Z","timestamp":1792057232000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.77969"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,15]]},"references-count":58,"alternative-id":["10.1002\/advs.77969"],"URL":"https:\/\/doi.org\/10.1002\/advs.77969","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,15]]},"assertion":[{"value":"2026-06-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e77969"}}