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

Affiliation

Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China. Electronic address: [Email]

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.

Keywords

G protein,G protein-coupled receptor,coupling specificity,intermediate state,protein engineering,

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