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Structural Insights into the Process of GPCR-G Protein Complex Formation.

Cell (2019-05-14)
Xiangyu Liu, Xinyu Xu, Daniel Hilger, Philipp Aschauer, Johanna K S Tiemann, Yang Du, Hongtao Liu, Kunio Hirata, Xiaoou Sun, Ramon Guixà-González, Jesper M Mathiesen, Peter W Hildebrand, Brian K Kobilka
ABSTRACT

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-Gsempty). Unfortunately, the β2AR-Gsempty 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-GsGDP) that may represent an intermediate on the way to the formation of β2AR-Gsempty 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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