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

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.
(Copyright © 2019 Elsevier Inc. All rights reserved.)