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

Liu, Xiangyu; Xu, Xinyu; Hilger, Daniel; Aschauer, Philipp; Tiemann, Johanna K S; Du, Yang; Liu, Hongtao; Hirata, Kunio et al. · Cell · 2019

basic_science · Level V

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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-Gs<sup>empty</sup>). Unfortunately, the β2AR-Gs<sup>empty</sup> 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<sup>GDP</sup>) that may represent an intermediate on the way to the formation of β2AR-Gs<sup>empty</sup> 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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