Structures of the Rhodopsin-Transducin Complex: Insights into G-Protein Activation

Rhodopsin (Rho), a prototypical G-protein-coupled receptor (GPCR) in vertebrate vision, activates the G-protein transducin (G_T) by catalyzing GDP-GTP exchange on its α subunit (Gα_T). To elucidate the determinants of G_T coupling and activation, we obtained cryo-EM structures of a fully functional, light-activated Rho-G_T complex in the presence and absence of a G-protein-stabilizing nanobody. The structures illustrate how G_T overcomes its low basal activity by engaging activated Rho in a conformation distinct from other GPCR-G-protein complexes. Moreover, the nanobody-free structures reveal native conformations of G-protein components and capture three distinct conformers showing the Gα_T helical domain (αHD) contacting the Gβγ subunits. These findings uncover the molecular underpinnings of G-protein activation by visual rhodopsin and shed new light on the role played by Gβγ during receptor-catalyzed nucleotide exchange.