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 alpha subunit (G alpha(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 GMT helical domain (alpha HD) contacting the G beta gamma subunits. These findings uncover the molecular underpinnings of G-protein activation by visual rhodopsin and shed new light on the role played by G beta gamma during receptor-catalyzed nucleotide exchange.