Analysis of β 2 AR-G s and β 2 AR-G i complex formation by NMR spectroscopy

作者：Xiuyan Ma, Yunfei Hu, Hossein Batebi, Jie Heng, Jun Xu, Xiangyu Liu, Xiaogang Niu, Hongwei Li, Peter W. Hildebrand, Changwen Jin, Brian K. Kobilka · 发表于：Proceedings of the National Academy of Sciences · 年份：2020 · DOI：10.1073/pnas.2009786117 · 被引用次数：86 · 研究领域：Receptor Mechanisms and Signaling、Protein Structure and Dynamics、Protein Kinase Regulation and GTPase Signaling

Significance Recent structures of GPCRs in complex with G proteins provide important insights into G protein activation by family A and family B GPCRs; however, important questions remain. We don’t fully understand the mechanism of G protein coupling specificity or coupling promiscuity of some GPCRs. The β 2 AR preferentially couples to G s and less efficiently to G i , yet β 2 AR-G i coupling has been shown to play important roles in cardiac physiology. To better understand the structural basis for the preferential coupling of the β 2 AR to G s over G i , we used NMR spectroscopy and supporting MD simulations to study the conformational changes in the intracellular surface of the β 2 AR. These studies reveal a distinct difference in intracellular loop 2 interactions with G s and G i1 .