an α-helix toward the β-pleated sheet. The α-helix is flexible in closed channels. When an α-helix of a CNGA1 subunit is in close proximity to another α-helix, they form intersubunit disulfide bonds. This occurs mainly in closed channels, inhibiting movement of the α-helix towards the β-pleated sheet. When a ligand binds to the β-pleated sheet, this bound cyclic nucleotide stabilizes the movement of the α-helix toward the β-pleated sheet in each subunit, pulling the α-helices away from each other. C-linker The C-linker is a region that connects the CNBD to the S6 segment. The C-linker region contributes to the contact between channel subunits as well as promotes tetramerization, the forming of tetramers. There are many residues that play a role in modulation of CNG channels. This process uses metals such as nickel, zinc, copper, and magnesium. The C-linker region is involved in the coupling of ligand binding to the opening of the pore. The C linker region forms disulfide bonds with N-terminal regions. Disulfide bonds alter the channel function therefore they most likely lie close to the tertiary structure. Disulfide bonds decrease the free energy of the open state compared to the closed state. The specific cysteine residue C481 on the C-linker region is located only a few amino acids away from the binding domain. In the closed state C481 is nonreactive; C481 must undergo a conformational change so that it is accessible for the opening of the channel. Disulfide bonds form between neighboring subunits and C481. Simultaneously there is a C35 cysteine residue at the N-terminal of the C-linker region that can reach two C481 residues, making a favorable disulfide bond compared to a C481-C481 bond. S6 region Spontaneous disulfide bond formation is state-dependent, implying that the conformational change in the helix bundle is affiliated with channel gating. When the CNG ion channels are closed, the cytoplasmic ends of the S6 helices are in close proximity to each other. Small cations are able to move through an opening, which implies that the gate is beyond the helix bundle and that S6 helices are in conjunction with conformational changes in the selectivity filter. P region The P region forms a loop, the pore loop, connecting the S5 and S6 regions, which extend to the central axis of the channel. Ionic properties are determined by the residues in the loop between S5 and S6 transmembrane segments. The P region dictates the