Structural Insights into the Process of GPCR-G Protein Complex Formation.Liu, X., Xu, X., Hilger, D., Aschauer, P., Tiemann, J.K.S., Du, Y., Liu, H., Hirata, K., Sun, X., Guixa-Gonzalez, R., Mathiesen, J.M., Hildebrand, P.W., Kobilka, B.K.
(2019) Cell 177: 1243-1251.e12
- PubMed: 31080070
- DOI: https://doi.org/10.1016/j.cell.2019.04.021
- Primary Citation of Related Structures:
- PubMed 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 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.
Institute for Molecular Bioscience, University of Graz, Humboldtstrasse 50/3, 8010 Graz, Austria.