Analysis of β <sub>2</sub> AR-G <sub>s</sub> and β <sub>2</sub> AR-G <sub>i</sub> complex formation by NMR spectroscopy
Xiuyan Ma, Yunfei Hu, Hossein Batebi, Jie Heng, Jun Xu, Xiangyu Liu, Xiaogang Niu, Hongwei Li, Peter W. Hildebrand, Changwen Jin, Brian K. Kobilka
Abstract
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 .