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Mol Cell. 2019 Aug 22;75(4):781-790.e3. doi: 10.1016/j.molcel.2019.06.007. Epub 2019 Jul 9.

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

Author information

1
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
2
Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
3
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA; Department of Molecular Medicine, Cornell University, Ithaca, NY 14853, USA. Electronic address: rac1@cornell.edu.
4
Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: yiorgo@stanford.edu.

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 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.

KEYWORDS:

G-protein; GPCR; GPCR-G-protein complex; cryo-EM; phototransduction; rhodopsin; transducing

PMID:
31300275
PMCID:
PMC6707884
[Available on 2020-08-22]
DOI:
10.1016/j.molcel.2019.06.007

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