“…The aN/b1 hinge and b1 strand at the amino terminus of the Ras-like domain links ICL2 with the P loop that binds the diphosphate of GDP (Figures 1C and 1D). Much has been learned about the detailed structural features and conformational dynamics of these two allosteric pathways using a variety of biophysical, biochemical, and computational approaches on different GPCR-G protein pairs (Alexander et al, 2014;Dror et al, 2015;Kaya et al, 2014;Moro et al, 1993;Nanoff et al, 2006;Oldham et al, 2006Oldham et al, , 2007Scheerer et al, 2009;Van Eps et al, 2011;Yano et al, 2017;Zhou et al, 1999). Nevertheless, understanding the temporal sequence of these substantial conformational changes during GPCR-mediated G protein activation are likely to provide additional insights into GPCR-G protein coupling selectivity (Preininger et al, 2013).…”