Fig. 4: Intracellular loops 2 and 3 guide the formation of specific intermediate states.
From: Snapshots of the dynamic basis of NTSR1 G protein subtype promiscuity
a, Molecular dynamics simulation results from n = 5 independent runs for the NTSR1–Gi1 NC-closed-GTP structure (turquoise traces) and the equivalent complex with MOR (green traces). The distances between ICL2 and the β2–β3 loop (left) and between ICL3 and the α4 helix (right) are used as a metric for whether the complex resembles the C-closed-GTP or NC-closed-GTP state. b, Cartoon of the kinetic bioluminescence resonance energy transfer (BRET) assay design. c, Kinetic BRET traces for the NTSR1 and MOR constructs tested in this work. WT, wild type. d, Heat maps of kinetic BRET assay results examining Gi and Gq signalling for NTSR1 and MOR with ICL2 and/or ICL3 swapped. Experiments were performed with three (NTSR1) or four (MOR) independent experiments with four technical replicates each. e, Cartoon of the ICL2 point mutation locations and heat maps of kinetic BRET assay results examining Gi and Gq signalling for NTSR1 ICL2 point mutants. Experiments were performed with three (NTSR1) or four (MOR) independent experiments with four technical replicates each.
