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

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

SUBMITTER: Gao Y

PROVIDER: S-EPMC6707884 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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

Gao Yang Y Hu Hongli H Ramachandran Sekar S Erickson Jon W JW Cerione Richard A RA Skiniotis Georgios G

Molecular cell 20190709 4

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 ...[more]

PMID: 31300275

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