The overall Josephin fold is conserved between members of the MJD family. Josephin-2 (cyan) is shown superposed on ataxin-3 (magenta; panel A) and AT3L (blue; panel B). (C) A reversed view of the superposed Josephin-2 and ataxin-3 structures, showing the “rear” surface of the molecules, i.e. the opposite face from the surface containing the active site. The black circle indicates Site 2 of ataxin-3, with ataxin-3’s Tyr-27, Phe-28, and Trp-87 residues shown as yellow sticks. (D) Electrostatic surface representations of ataxin-3 and Josephin-2, shown in the same orientation as panel C. The black circles show the position of Site 2 in ataxin-3, and of the corresponding region in Josephin-2, highlighting how the surface characters of the two proteins differ at this position. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)