Supplementary Figure 3: Comparison of DEDD exo- and pseudonucleases.

a) Structure-based sequence alignment of the EXO and EXO-like domains of Drosophila Exu (Exu_Dm) and of structurally similar 3'-5' DEDD exonucleases, mouse Trex1 (Trex1_Mm) and E. coli RNaseT (RNaseT_Ec). Secondary structure elements are shown above the sequences, in red for Exu and in dark gray for Trex1. Conserved residues are highlighted in dark gray. Blue boxes indicate EXO signature motifs, while signature catalytic residues are marked in red. Brackets indicate protein-specific insertions that are hidden for clarity. The positions of Exu β-hairpin insertion, loop1 and linker are indicated. For each protein, residues involved in homodimerization are highlighted in light blue.

b-e) Cartoon (left) and surface (middle and right) representation of the indicated protein structures. Exu³³³ (b) and Trex1 (d) are in the same orientation as in Fig. 2a, b. Residues in the (pseudo-)catalytic site are shown as sticks; ions (Zn²⁺ in (c) and Mn²⁺ in (d)) are represented as spheres. Protein-specific features are highlighted in red: linker helix and β-hairpin insertion in Exu (b); Zn²⁺ coordinating extension in Maelstrom (Mael) (c). Surface is colored according to the electrostatic charge, with the (pseudo)-catalytic site boxed in yellow. Structural alignment was done with cealign in Pymol (v 1.7.6.0). Scale of electrostatic charge distribution is the same for all domains (-5 to +5 kT/e).