The SPR2 C-terminal domain is an α-solenoid helix-turn-helix domain containing seven helices.

(A) Structure of the A.t. SPR2 C-terminal domain shown in cartoon format. The seven core helices of the domain (α1-α7) are colored across the spectrum. A final helix, α8, packs against the domain, but is not conserved across SPR2 homologs, and thus is not considered part of the core domain. Six of the helices form helix-turn-helix pairs: 2α-3α, 4α-5α, and 6α-7α. View at left is rotated 90° about the y-axis to generate the view at right. Relative dimensions of the domain are indicated. (B) Conserved residues in the α2-α3 region contribute the domain’s hydrophobic core. Residues are shown in stick format, with conservation colored as in Fig 1B, with final 2mF_o-DF_c electron density shown in blue, contoured at 1.0 σ. Two SeMet residues used in phasing are indicated. (C) Structural comparison of canonical ARM, HEAT, and FANC repeats (top row) versus SPR2 C-terminal domain helix-turn-helix pairs α2-α3, α4-α5, and α6-α7 (bottom row). The representative HEAT repeat is from the structure of human PP2A PR65α (PDB ID 1B3U), repeat number 11 [38], with the canonical kink in helix A delineated. The representative ARM repeat is from the structure of mouse β-catenin (PDB ID 3BCT), repeat number 2 [39], with the canonical additional N-terminal helix H1 delineated. The representative FANC repeat is from the structure of human FANCE (PDB ID 2ILR), repeat number 5 [40]. (D-E) Splayed view of the SPR2 C-terminal domain, showing residues (primarily hydrophobic) buried in the core, contributed from helices α1, α2, α4, α6, and α8 (D), and helices α3, α5, and α7 (E), which respectively constitute opposite regions of the domain. The side chains of core residues are shown in stick format, colored based on the conservation delineated in Fig 1B.