Fig. 5: Mechanistic and structural implications of the proline switch in SthK.
From: Prolyl isomerization controls activation kinetics of a cyclic nucleotide-gated ion channel
a Model of the modulatory prolyl isomerization in SthK used for simulations as shown in (b, c), and Supplementary Fig. 9f–i. Transitions in gray were omitted for the simulations since their inclusion does not change the outcome and to reduce the number of parameters. b Simulated, macroscopic activation time courses of 10,000 channels upon ligand application (100 µM cAMP) according to the model shown in (a). c Comparison of the theoretical dose-response curves of WT SthK (black), WT SthK + PPIase (orange), and SthK P300A (blue) after 2.5 s activation by cAMP (same condition as the experimental stopped-flow assay shown in Fig. 3d). Conditions and results of simulations are given in Supplementary Table 3 and 4. d Modeled cis Pro300 (left panel) in comparison to trans Pro300 (right panel) in WT SthK (PDB: 6CJU, EMDB: 7484). e Propagation of conformational changes during gating of SthK through one CNBD and along the subunit interface. The closed state of SthK P300A is shown in blue, the putatively active state in yellow.
