1.A.1.5.17
Cyclic nucleotide-gated K⁺channel, SthK, of 430 aas, probably with 6 TMSs in a 2 + 2 + 1 + P-loop + 1 TMS arrangement.  The channel is activated by cAMP, not by cGMP, and is highly specific for K⁺ over Na⁺.  It has a C-terminal hydrophilic cAMP-binding domain linked to the 6 TMS channel domain (Brams et al. 2014). An SthK C-linker domain is essential for coupling cyclic nucleotide binding to channel opening (Evans et al. 2020). An agonist-dependent conformational change in which residues of the B'-helix displayed outward movement with respect to the symmetry axis of the channel in the presence of cAMP was observed, but not with the partial agonist, cGMP. This conformational rearrangement was observed both in detergent-solubilized SthK and in channels reconstituted into lipid nanodiscs. In addition to outward movement of the B'-helix, channel activation involves upward translation of the cytoplasmic domain with formation of state-dependent interactions between the C-linker and the transmembrane domain (Evans et al. 2020). Three-deminsional structures are available (7RSY_A-D). SthK is active in a sparsely tethered lipid bilayer membranes (Andersson et al. 2023).