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

ABSTRACT: The crystal structure of the ?2-adrenergic receptor (?2AR) bound to the G protein adenylyl cyclase stimulatory G protein (Gs) captured the complex in a nucleotide-free state (?2AR-Gsempty). Unfortunately, the ?2AR-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 ?2AR and GDP-bound Gs protein (?2AR-GsGDP) that may represent an intermediate on the way to the formation of ?2AR-Gsempty and may contribute to coupling specificity. Here we present a structure of the ?2AR in complex with the carboxyl terminal 14 amino acids from G?s along with the structure of the GDP-bound Gs heterotrimer. These structures provide evidence for an alternate interaction between the ?2AR and Gs that may represent an intermediate that contributes to Gs coupling specificity.

SUBMITTER: Liu X 

PROVIDER: S-EPMC6991123 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature