Schemes showing the domain architecture of SMG6, SMG5 and SMG7. In the structures, the protein domains are coloured according to their primary structure scheme. (A) Structure of the tetratricopeptide (TPR) domain of SMG6 with a 14-3-3-like module (dark red) involved in binding phosphorylated serine/threonine residues of UPF1 and α-helical hairpins (orange) (PDB ID: 4UM2) [71]. The close-up view shows the phosphoserine-binding pocket of SMG6 with key residues highlighted as sticks. (B) Structure of SMG6's PIN domain (chocolate) (PDB ID: 2HWW) [115]. The close-up view of the nuclease active site highlights the canonical catalytic triad of acidic residues (D1251, D1353, D1392). (C) Structure of SMG5's PIN domain (red) (PDB ID: 2HWY) [115]. The close-up view shows the inactive site in SMG5 comprising only one aspartate (D860, I948, V983). (D) Structure of the heterodimer of the TPR domain of SMG5 with a 14-3-3-like module (red) and α-helical hairpins (light red) and the TPR domain of SMG7 (14-3-3-like module, beige; α-helical hairpins, brown) (PDB ID: 3ZHE) [113]. SMG5 and SMG7 interact via their 14-3-3-like modules. The close-up view shows the phosphoserine-binding pocket of SMG5 with key residues highlighted as sticks. (E) Structure of the TPR domain of SMG7 with its 14-3-3-like module (beige) and α-helical hairpins (brown) (PDB ID: 1YA0) [116]. The close-up view shows the phosphoserine-binding pocket of SMG7 with key residues and a phosphate ion highlighted as sticks.