Open AccessCryo-EM structure of human rhodopsin bound to an inhibitory G protein
Author(s) -
Ying Kang,
Oleg Kuybeda,
Parker W. de Waal,
Somnath Mukherjee,
Ned Van Eps,
Przemysław Dutka,
Xuemei Zhou,
Alberto Bartesaghi,
Satchal K. Erramilli,
Takefumi Morizumi,
Xin Gu,
Yuanyuan Yin,
Ping Liu,
Yi Jiang,
Xing Meng,
Gongpu Zhao,
Karsten Melcher,
Oliver P. Ernst,
Anthony A. Kossiakoff,
Sriram Subramaniam,
H. Eric Xu
Publication year - 2018
Publication title -
nature
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 15.993
H-Index - 1226
eISSN - 1476-4687
pISSN - 0028-0836
DOI - 10.1038/s41586-018-0215-y
Subject(s) - rhodopsin , arrestin , transmembrane domain , g protein coupled receptor , receptor , transmembrane protein , g protein , protein subunit , microbiology and biotechnology , biology , helix (gastropod) , protein structure , biochemistry , biophysics , chemistry , gene , retinal , ecology , snail
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 G s (stimulatory) and G i (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 G i are mediated by the C-terminal helix of the G i 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, G i -bound and arrestin-bound forms of rhodopsin with inactive and G s -bound forms of the β 2 -adrenergic receptor provide a foundation to understand the unique structural signatures that are associated with the recognition of G s , G i and arrestin by activated G-protein-coupled receptors.