Fig. 5: Structural characterization of PrefCoupGαi2 mutant clusters.
From: Multiple intramolecular triggers converge to preferential G protein coupling in the CB2R
A Perturbation map of the ACN induced by PrefCoupGαi2 mutants. Top interaction features for PrefCoupGαi2 cluster 1 (dark brown), 2 (light brown) and 3 (orange). The interactions are plotted together with the computed ACNs for the WT CB2R. For instance, such depiction highlights allosteric connections (brown to orange) to the ligand-stabilized ACN (light and dark blue) that are perturbed in preferential Gαi2 coupling of the CB2R (PDB ID: 6KPC). B–D Mutant impact on highly conserved receptor regions for clusters 1 to 3. Non-conserved residues which are part of the modulation are represented as white spheres whereas the corresponding contact is highlighted as a cylinder indicating the change of contact stability compared to conserved coupling (CoupGαi2_βarr1): navy blue corresponds to increased interaction stability in the PrefCoupGαi2 mutants, yellow indicates decreased interaction stability. The thickness of the cylinders is proportional to the absolute value of the coefficient for that interaction in the logistic regression model (PDB ID: 6KPC). E Summary of mutant-perturbed domains of high conservation (i.e., CWxP, Na+ site, NPxxY, DRY) for PrefCoupGαi2 mutant clusters 1 to 3. For each cell, we indicate the implicated residues in the contact and the corresponding contact frequency for each pair of residues. Each cell is colored according to the prediction of a logistic regression model: more stable contacts (navy blue) and less stable contacts (yellow) of PrefCoupGαi2 compared to CoupGαi2_βarr1 mutants. Further details about differences in contact frequencies between PrefCoupGαi2 and CoupGαi2_βarr1 mutants are plotted in Supplementary Fig. 5. Source data are provided as a Source data file.
