Extended Data Fig. 6: Time-traces of selected parameters related to signal transfer (Fig. 5) for simulation runs of the β2AR-GsGDP (run 2, blue), the β2AR-GsGDPspawns (run 5, green) and all runs of the GsGDP simulations (black).
From: Mechanistic insights into G-protein coupling with an agonist-bound G-protein-coupled receptor
A) Residue-residue distances involved in the suggested path 1 (Fig. 5), where a shift of F212β2 toward α1 leads to breakage of αF-α1, switchI-GDP and TCAT (β6-α5 loop)-αF interactions (residues are tagged with their CGN-labels6). B) Residue-residue distances involved in the suggested path 2, where ICL2 interacts with the middle of α5 and β6 (first three rows), leading to the displacement of αG (second three panels). Residues are tagged with the Ballesteros-Weinstein labels91,92. C) Solvent-Accessible-Surface-Area, SASA (in nm2) of GDP for all runs of all simulations. The panels on the left show the SASA time-traces for all trajectories, while the panels on the right show the per-trajectory SASA distributions. Both in the time-traces and in the distributions, we see increased SASA when β2AR is present. Moreover, we see sharp increases when the simulation enters the β2AR-GsGDP intermediate state A (solid blue line, ca. 2 µs) and an even larger increase when entering the β2AR-GsGDP intermediate state 5 (solid green line, ca 10 µs) (see Extended Data Fig. 3E for state time traces). Traces have been smoothed using a moving window of 100 ns, with the raw data shown as a gray backdrop for the blue and green (the backdrop of the black lines has been left out for clarity).
