The coiled-coils of TRPM channels. (A) Helical wheel representation of parallel (left) and antiparallel (right) tetrameric coiled-coils. The “N” or “C” in each wheel indicates whether the N or C terminus, respectively, of the α-helix points toward the viewer. Darker lines are in front and lighter ones are in the back. In both coiled-coils, the a and d residues of the heptad repeats form the core, whereas the e and g residues form peripheral interactions. However, the details of the interactions are different. In a parallel coiled-coil, each layer of hydrophobic interactions consists of either four a or four d residues. In contrast, each antiparallel layer consists of two d and two a residues. (B) Sequence alignment of the predicted coiled-coil sequences of human TRPM channels. The sequence of the rat TRPM7 coiled-coil, for which the structure is available, is also included at the top. a and d position residues are shaded. The dendrogram was generated by ClustalW using an alignment of whole TRPM sequences. (C) Diagram of TRPM7 displaying the available structural information. Similarly to Fig. 1, only two of the four channel subunits are illustrated for clarity (green and blue, respectively), except for the coiled-coil structure where all four strands are shown. Note that the transmembrane domain would have fourfold rotational symmetry perpendicular to the membrane (gray shading), whereas the coiled-coil and α-kinase domains only have twofold symmetry. Shape sizes approximate the number of residues in each region, and the size (in number of amino acid residues [aa]) is indicated for the blue subunit. The approximate boundaries, in residue numbers, of different domains are also indicated.