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

Yang Gao, Hongli Hu, Sekar Ramachandran, Jon W Erickson, Richard A Cerione, Georgios Skiniotis

Molecular cell 2019 Aug 22

filter terms:

Rhodopsin (Rho), a prototypical G-protein-coupled receptor (GPCR) in vertebrate vision, activates the G-protein transducin (GT) by catalyzing GDP-GTP exchange on its α subunit (GαT). To elucidate the determinants of GT coupling and activation, we obtained cryo-EM structures of a fully functional, light-activated Rho-GT complex in the presence and absence of a G-protein-stabilizing nanobody. The structures illustrate how GT 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 GαT 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. Copyright © 2019 Elsevier Inc. All rights reserved.

Citation

Yang Gao, Hongli Hu, Sekar Ramachandran, Jon W Erickson, Richard A Cerione, Georgios Skiniotis. Structures of the Rhodopsin-Transducin Complex: Insights into G-Protein Activation. Molecular cell. 2019 Aug 22;75(4):781-790.e3