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Nature. 2018 Jun;558(7711):553-558. doi: 10.1038/s41586-018-0215-y. Epub 2018 Jun 13.

Cryo-EM structure of human rhodopsin bound to an inhibitory G protein.

Author information

1
Center for Cancer and Cell Biology, Innovation and Integration Program, Van Andel Research Institute, Grand Rapids, MI, USA.
2
Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
3
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, USA.
4
Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.
5
Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
6
University of Chinese Academy of Sciences, Beijing, China.
7
Key Laboratory of Receptor Research, VARI-SIMM Center, Center for Structure and Function of Drug Targets, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
8
David Van Andel Advanced Cryo-Electron Microscopy Suite, Van Andel Research Institute, Grand Rapids, MI, USA.
9
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
10
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, USA. koss@bsd.uchicago.edu.
11
Institute for Biophysical Dynamics, University of Chicago, Chicago, IL, USA. koss@bsd.uchicago.edu.
12
Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA. ss1@nih.gov.
13
Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA. ss1@nih.gov.
14
Center for Cancer and Cell Biology, Innovation and Integration Program, Van Andel Research Institute, Grand Rapids, MI, USA. eric.xu@vai.org.
15
Key Laboratory of Receptor Research, VARI-SIMM Center, Center for Structure and Function of Drug Targets, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. eric.xu@vai.org.

Abstract

G-protein-coupled receptors comprise the largest family of mammalian transmembrane receptors. They mediate numerous cellular pathways by coupling with downstream signalling transducers, including the hetrotrimeric G proteins Gs (stimulatory) and Gi (inhibitory) and several arrestin proteins. The structural mechanisms that define how G-protein-coupled receptors selectively couple to a specific type of G protein or arrestin remain unknown. Here, using cryo-electron microscopy, we show that the major interactions between activated rhodopsin and Gi are mediated by the C-terminal helix of the Gi α-subunit, which is wedged into the cytoplasmic cavity of the transmembrane helix bundle and directly contacts the amino terminus of helix 8 of rhodopsin. Structural comparisons of inactive, Gi-bound and arrestin-bound forms of rhodopsin with inactive and Gs-bound forms of the β2-adrenergic receptor provide a foundation to understand the unique structural signatures that are associated with the recognition of Gs, Gi and arrestin by activated G-protein-coupled receptors.

PMID:
29899450
DOI:
10.1038/s41586-018-0215-y
[Indexed for MEDLINE]

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