Structural model of the c-di-GMP regulation.

<p>(A) Ribbon representation of transmembrane segments of two opposing subunits and the C-linker/CNBDs of the two subunits adjacent to them from the full-length structure of HCN1 channels [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0185359#pone.0185359.ref045" target="_blank">45</a>]. The transmembrane segments of the subunits containing the C-linker/CNBDs shown in the figure and the C-linker/CNBDs of the subunits containing transmembrane segments shown in the figure are omitted for clarity. In the crystal structure C-linkers are making direct contacts with S4-S5 linkers and HCN domains from only the adjacent subunits. Transmembrane segments (TM) are shown in grey, S4-S5 linkers and HCN domains are orange, C-linkers are red, β-roll and helices A, P and B are blue, and the C-helix and the distal C-terminus are green. cAMP bound inside the β-roll cavity is yellow. c-di-GMP placed in the proposed CLP site is cyan. (B) Structural alignment of the C-linker/CNBD from the full-length HCN1 structure [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0185359#pone.0185359.ref045" target="_blank">45</a>] shown in gray and isolated C-linker/CNBD of HCN2 channels [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0185359#pone.0185359.ref015" target="_blank">15</a>] shown in magenta.