Open AccessStructural Insights into the Process of GPCR-G Protein Complex Formation
Author(s) -
Xiangyu Liu,
Xinyu Xu,
Daniel Hilger,
Philipp Aschauer,
Johanna K. S. Tiemann,
Yang Du,
H Liu,
Kunio Hirata,
Xiaoou Sun,
Ramon GuixàGonzález,
Jesper Mosolff Mathiesen,
Peter W. Hildebrand,
Brian K. Kobilka
Publication year - 2019
Publication title -
cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 26.304
H-Index - 776
eISSN - 1097-4172
pISSN - 0092-8674
DOI - 10.1016/j.cell.2019.04.021
Subject(s) - biology , adenylyl cyclase , g protein coupled receptor , gs alpha subunit , g protein , coupling (piping) , amino acid , microbiology and biotechnology , receptor , complex formation , peptide sequence , biochemistry , gene , mechanical engineering , inorganic chemistry , chemistry , engineering
The crystal structure of the β2-adrenergic receptor (β2AR) bound to the G protein adenylyl cyclase stimulatory G protein (Gs) captured the complex in a nucleotide-free state (β2AR-Gs empty ). Unfortunately, the β2AR-Gs empty complex does not provide a clear explanation for G protein coupling specificity. Evidence from several sources suggests the existence of a transient complex between the β2AR and GDP-bound Gs protein (β2AR-Gs GDP ) that may represent an intermediate on the way to the formation of β2AR-Gs empty and may contribute to coupling specificity. Here we present a structure of the β2AR in complex with the carboxyl terminal 14 amino acids from Gαs along with the structure of the GDP-bound Gs heterotrimer. These structures provide evidence for an alternate interaction between the β2AR and Gs that may represent an intermediate that contributes to Gs coupling specificity.
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