000126902 001__ 126902 000126902 005__ 20240731103309.0 000126902 0247_ $$2doi$$a10.1016/bs.pmbts.2022.06.015 000126902 0248_ $$2sideral$$a131628 000126902 037__ $$aART-2023-131628 000126902 041__ $$aeng 000126902 100__ $$0(orcid)0000-0002-7183-2758$$aCarrión Antolí, Ángela$$uUniversidad de Zaragoza 000126902 245__ $$aStructural insights into promiscuous GPCR-G protein coupling 000126902 260__ $$c2023 000126902 5060_ $$aAccess copy available to the general public$$fUnrestricted 000126902 5203_ $$aG protein-coupled receptors (GPCRs) transduce extracellular signals across biological membranes by activating heterotrimeric Gαβγ proteins. There are 16 different human Gα proteins grouped into four families (GS, Gi/O, Gq/11 and G12/13), each one activating different signaling cascades. Around 50% of non-olfactory GPCRs activate more than one type of Gα proteins with different efficacy and kinetics, triggering a fingerprint-like signaling profile. In this chapter we review the GPCR-G protein promiscuity landscape and discuss recent structures of GPCRs coupled to different Gα proteins. Overall, the size and shape of the intracellular cavity (determined by the extent of outward movement of TM6) is maintained when the receptor is coupled to different Gα proteins, and is determined by the type of primary Gα coupling. The “sub-optimal” secondary Gα coupling is further supported by interactions with the intracellular loops, with ICL2 and ICL3 having a relevant role in promiscuous couplings. 000126902 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/ 000126902 592__ $$a0.133$$b2023 000126902 593__ $$aMolecular Medicine$$c2023$$dQ4 000126902 593__ $$aMolecular Biology$$c2023$$dQ4 000126902 594__ $$a5.0$$b2023 000126902 655_4 $$ainfo:eu-repo/semantics/review$$vinfo:eu-repo/semantics/acceptedVersion 000126902 700__ $$aMallor Franco, Jorge 000126902 700__ $$0(orcid)0000-0003-3785-298X$$aArroyo Urea, Sandra$$uUniversidad de Zaragoza 000126902 700__ $$0(orcid)0000-0002-4254-3148$$aGarcía Nafría, Javier$$uUniversidad de Zaragoza 000126902 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole. 000126902 773__ $$g195, 137-152 (2023)$$pPROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE$$tPROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE$$x1877-1173 000126902 8564_ $$s9552801$$uhttps://zaguan.unizar.es/record/126902/files/texto_completo.pdf$$yPostprint 000126902 8564_ $$s569301$$uhttps://zaguan.unizar.es/record/126902/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint 000126902 909CO $$ooai:zaguan.unizar.es:126902$$particulos$$pdriver 000126902 951__ $$a2024-07-31-09:38:56 000126902 980__ $$aARTICLE