PMC

Structural comparison of the C-linker regions and quaternary arrangement of the C-linker/CNBHDs of zELK and HCN2 channels. a, A dimer formed by the C-linker/CNBHD of zELK channels viewed perpendicular (left) and parallel (right) to the two-fold axis. b, A tetramer formed by the C-linker/CNBD of HCN2 channels viewed perpendicular (left) and parallel (right) to the four-fold axis. c, Superposition of the ribbon representations of the C-linker/CNBHDs monomers of zELK (yellow) and HCN2 channels (magenta) using the alignment of the α-carbons of CNBDs of these structures. d, Superposition of the “elbow-on-the-shoulder” interface of zELK (blue “elbow”, yellow “shoulder”) and HCN2 channels (grey “elbow”, magenta “shoulder”).

Topology and electrophysiological properties of zELK channels. a, Cartoon of two of the four subunits of zELK channels. The pore forming loop and S5–S6 transmembrane domains are grey. The N-terminal α-helix and PAS domain are magenta. The “elbow” and “shoulder” regions of the C-linker are represented by the red and pink cylinders respectively. The αC-helix, represented by a cylinder, is green and the rest of the CNBHD is blue. b, Currents for zELK channels recorded in the inside-out patch configuration.

Structure of the C-linker/CNBHD. a, Ribbon representation of a monomer of the C-linker/CNBHD of zELK channels. b, Alignment of the CNBHD of zELK (the αC-helix is green and the rest is blue) and HCN2 (grey) channels. cAMP in the HCN2 structure is yellow. c, d, Electrostatic potential surface of the CNBHD of zELK (c) and HCN2 channels (d), viewed in the same orientation as in . e, Residues in the β-roll cavity interacting with residues Y740 and L742 of the intrinsic ligand. Dashed lines show both polar and non-polar interactions. cAMP from the HCN2 structure is shown in yellow. f, Representative conductance-voltage relations for wild-type (black), Y740A mutant (blue), and Δ740-742 mutant (green) zELK channels.