Tsai, Ching-JuMarino, JacopoAdaixo, RicardoPamulal, FilipMuehle, JonasMaeda, ShojiFlock, TilmanTaylorn, Nicholas M. I.Mohammed, InayatullaMatile, HuguesDawson, Roger J. P.Deupi, XavierStahlberg, HenningSchertler, Gebhard2020-02-132020-02-132020-02-132019-06-2810.7554/eLife.46041https://infoscience.epfl.ch/handle/20.500.14299/165319One of the largest membrane protein families in eukaryotes are G protein-coupled receptors (GPCRs). GPCRs modulate cell physiology by activating diverse intracellular transducers, prominently heterotrimeric G proteins. The recent surge in structural data has expanded our understanding of GPCR-mediated signal transduction. However, many aspects, including the existence of transient interactions, remain elusive. We present the cryo-EM structure of the light-sensitive GPCR rhodopsin in complex with heterotrimeric Gi. Our density map reveals the receptor C-terminal tail bound to the G beta subunit of the G protein, providing a structural foundation for the role of the C-terminal tail in GPCR signaling, and of G beta as scaffold for recruiting G alpha subunits and G protein-receptor kinases. By comparing available complexes, we found a small set of common anchoring points that are G protein-subtype specific. Taken together, our structure and analysis provide new structural basis for the molecular events of the GPCR signaling pathway.text::journal::journal article::research article