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. 2018 Jul 31;7:e38433. doi: 10.7554/eLife.38433

Figure 1. TMC1 and TMEM16 proteins share a common fold.

(A) Hydrophobicity profiles for nhTMEM16 (gray) and mTMC1 (green) revealing conserved hydrophobic regions. Residues corresponding to mTMC1 TM helices are indicated with green bars and gray shading. (B) Hydrophobicity profiles for mTMEM16A (blue) and mTMC1 (green) revealing conserved hydrophobic regions. TM regions are indicated as in (A). (C) mTMC1, nhTMEM16 and mTMEM16A sequence alignment used to generate TMC1 models. Non-modeled residues are shown in gray without highlighting, while residues shown in the model are highlighted according to their properties; neutral in white, aromatic in yellow, polar in green, basic in blue and acidic in red. TMC1 secondary structure prediction (ssp) is shown at the top of the alignment and secondary structure information extracted from nhTMEM16 and mTMEM116A structures (dssp1 and dssp2, respectively) is included below the corresponding sequences. Grey rectangles indicate loops, pink rectangles β-strands, and α−helices are shown as green rectangles for TMC1, grey for nhTMEM16 and blue for mTMEM16A. Conserved TM helices are labeled and the six residues involved in calcium binding found in TMEM16 and absent in TMC proteins, are indicated with black arrowheads. The magenta arrowhead indicates the position of the Beethoven mutation in TMC1.

Figure 1.

Figure 1—figure supplement 1. Results from HHpred search for TMC1 templates.

Figure 1—figure supplement 1.

(A) Schematic representation of TMC1 templates identified using HHpred and color-coded based on whether the score is high (red), moderate (green) or low (blue). The two TMEM16 proteins (nhTMEM16, 4WIS and mTMEM16A, 5OYB) stand out as unique high-scoring templates for TMC1. (B) HHpred scores for the top 14 TMC1 templates.
Figure 1—figure supplement 2. Initial sequence alignments.

Figure 1—figure supplement 2.

Initial protein sequence alignment of TMC1 and nhTMEM16 (A) or TMC1 and mTMEM16A (B) obtained from HHpred and represented as in Figure 1C. (C) nhTMEM16 (PDB ID: 4WIS) and mTMEM16A (PDB ID: 5OYB) structural alignment obtained with TMalign. Cavity-lining helices TM4 and TM6 are indicated. (D) nhTMEM16 (gray) and mTMEM16A (blue) structural superimposition in ribbon representation revealing the major structural difference due to the rearrangement of TM4 and TM6 (red arrows).