Untethering the Nuclear Envelope and Cytoskeleton: Biologically Distinct Dystonias Arising from a Common Cellular Dysfunction

Figure 1

Schematic diagram of the AAA⁺ torsin protein family. The key features of torsinA, torsinB, torsin2, and torsin3 are shown, including the signal sequence (SS; turquoise), hydrophobic domain (Hypb; grey), and AAA⁺ domain (purple). The AAA⁺ domain of torsinA, illustrated in more detail, consists of Walker A/B (green) motifs, sensor I/II (orange) motifs, and six conserved cysteines (C). Also, the total number of amino acids (a.a.) for each protein and the overall percentage similarity with torsinA are indicated. In torsin2, the Hydb domain is absent and torsin3 has a longer Hydb domain. The 10 a.a. region in torsinA in which the glutamic acid deletion underlying DYT1 dystonia occurs is shown in detail. Conserved a.a. residues in this region in other members of the torsin family are underlined (figure revised from Jungwirth et al. [26] and Zhu et al. [54]).