Fig. 5: Putative mechanism of PIP2 inhibition.
From: PIP2 inhibits pore opening of the cyclic nucleotide-gated channel SthK
a Alignment of the PIP2 inhibited structure (grey) with SthK in the open conformation (blue, PDB: 7TJ6). Movements of the helices associated with channel opening are depicted by yellow arrows. The C-linker undergoes an upward movement leading to an outward rotation of the S6 helix that can only be facilitated by outward movements of the lower S4-S5 helices. b PIP2 binding in the closed state (top) and superimposed on the open state (bottom). In the closed state, Arg residues on S4 electrostatically coordinate PIP2 (green dashes) while in the open state the distance is too far. In addition, steric clashes are observed between PIP2 and the C-linker (red traffic circles). c Alignment of the SthK PIP2 binding site with the structure of human CNGA1 (PDB: 7LFT). Positively charged residues responsible for PIP2 binding in SthK are labelled and three of them are conserved in CNGA1.
