Fig. 1: The overall conformations of TM6s in active GPCRs.

a CB₁ and SMO example structures (left), conformations of TM6s of class A, B, and F GPCRs (right). Pro^6.50, Pro^6.47, and Pro/Phe^6.43, respectively, are shown as sticks, while receptors and G proteins are shown as cartoon (class A: green, class B: blue, SMO: violet, FZD₆: white, G_i: gray). In each structure, the kink in the TM6 is marked with a pink arrow. b Sequence alignment of human class F receptors (see also Supplementary Data 1). The conserved Pro^6.43 in FZDs is marked with a pink rectangle. The grey bars and violet shadings indicate the sequence conservation. The horizontal violet bar indicates the location of TM6. c Active and inactive structures of FZD₆ (left) and SMO (right). Active receptors are shown as white (FZD₆) and violet cartoon (SMO), and incative receptors as pink (FZD₆) and dark violet (SMO) cartoon. d, e TM6 angles throughout the MD trajectory. The angle is measured between the backbone nitrogen atoms of Leu/Ile^6.39, Pro/Phe^6.43, and Leu/Ala^6.47 in each MD frame. In d angles are averaged and given as mean ± SD, whereas in e each measured angle is given as a function of time. The simulation replicas 1 (blue) and 2 (dark gray) started from t = 0 ns are plotted starting from time point 0 and replicas 3 (light gray) and 4 (violet) started from t = 250 ns are plotted starting from time point 250. Thick traces indicate the moving average smoothed over a 1 ns window and thin traces the raw data.