Yeast Fis1ΔTM adopts a TPR-like fold. (a) Stereoview of the C^α trace of Fis1 with every 20th residue labeled. Note that no electron density was observed for residues 1–5, which are not depicted. (b) A stereoview cartoon of the Fis1 backbone with the autoinhibitory domain, or Fis1 arm, in blue and the remainder of the molecule rainbow colored from blue to red from the N-terminus to the C-terminus. The first tetratricopeptide repeat consists of helices 2–3 and the second repeat consists of helices 4–5. The bottom panel was obtained by a −60° rotation along the x axis of the structure in the top panel. This figure was generated in PyMOL (DeLano, 2002 ▶).

Multiple interactions contribute to stabilizing the Fis1 arm–concave surface interaction. (a) The final σ_A-weighted 2F _o − F _c electron-density map displaying residues 5–16 in the autoinhibitory Fis1 arm calculated at 1.75 Å resolution and contoured at 1σ. (b) Expanded view of the hydrogen-bonding interactions that serve to stabilize the Fis1 arm with α2 and α4 on the concave surface, involving Lys89 on α4 and the backbone carbonyls of Ala13, Ile50 and Lys51. These interactions stabilize the inhibitory state of the Fis1 arm. (c) The side-chain amide group of Gln112 forms reciprocal hydrogen bonds with the backbone amide of Trp7. This interaction is broken upon complexation (see text). This figure was generated in PyMOL (DeLano, 2002 ▶).

Structural comparisons of the autoinhibitory arm. (a) Superposition of the lowest-energy NMR-derived structure (PDB entry 1y8m; green) with that reported here (PDB entry 3o48; white) reveals differences in the orientation of the Fis1 arm that are quantified by DIMPLOT (Wallace et al., 1995 ▶) analysis of the NMR structure 1y8m (b) and the X-ray structure 3o48 (c). In (b) and (c) hydrogen bonds are shown by dashed lines (green) between Fis1-arm (green) and TPR (pink) residues. The length of the bond is indicated in the middle of the dashed line. Hydrophobic interactions are shown by spoked arcs between residues of the Fis1 arm (residues in black with red arcs and spokes) and TPR (residues in blue with pink arcs and spokes). Default criteria were used for determining hydrogen bonds and hydrophobic interactions (Wallace et al., 1995 ▶). (d) Superposition of Fis1 molecules from a complex with Caf4p (PDB entry 2pqr; red) with that reported here (PDB entry 3o48; white). Note that the ligand is not shown. (e) Superposition of Fis1 molecules from a complex with Mdv1p (PDB entry 2pqn; red) with that reported here (PDB entry 3o48, white). Note that the ligand is not shown. This figure was generated using PyMOL (DeLano, 2002 ▶).