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Figure 5 (A) One to four CaM molecules are bound to the CIRB binding sites of the tetrameric TRPC4 channel. 13% of particles are decorated with one (yellow), 35% with two (lilac), 31% with three (grey) and 20% with four CaM molecules (turquoise). (B) Side view of the CaM-bound TRPC4 density map (transparent) with the corresponding atomic model fitted inside, in which each protomer is colored differently. Position of the horizontal helix is indicated by black arrowhead. The bottom view of the atomic model is shown in the right panel. A schematic representation for both views is provided next to the atomic models. CaM is colored in orange. (C) Close-up of the indicated region in (B), showing the CaM binding region (left panel). CaM is colored in orange, TRPC4 in green. Positions of the horizontal helix and loop region 273–277 are indicated by black and blue arrowhead, respectively. Important and the predicted interacting residues of TRPC4 and CaM based on our model are highlighted in the right panel. (D) TRPC4 (cartoon representation) and CaM (surface representation) are colored according to hydrophobicity. There is a central hydrophobic cavity in CaM that is surrounded by hydrophilic residues in its periphery. The complementary binding region of TRPC matches this profile. (E) The C-terminal helix (red), the rib-helix (red-orange), the horizontal helix (purple), the TRP helix (orange) and the pore-forming helices (blue) of a single TRPC4 promoter are shown before (left panel) and after CaM binding (right panel). CaM binding stabilizes the previously disordered region connecting the rib-helix and horizontal/TRP-helix. LMNG – lauryl maltose neopentyl glycol.