Figure 2.

Out‐of‐register mating sheet architecture formed by the segment SOD1 28–38 with the familial mutation G37R. (A) Crystal structure of the segment 28–38 with familial mutation G37R at 1.8 Å resolution reveals a novel architecture of highly curved sheets mating via stacking of aromatic side chains of W32 residue. The curved architecture enables both faces of the sheets to exclude water molecules as shown here in views perpendicular (left) and parallel (right) to the fibril axis. (B) The weak interface composed of W32 stacking forms a pocket in which small molecules can bind. Orange G (shown in orange sticks) was cocrystallized and found to bind in the pocket. (C) Electron density map contoured at 1.0 σ showing clear density for orange G. (D) Orange G stabilizes the assembly by forming a network of hydrogen bonds with K30 and W32 of one sheet and K30 of the opposing sheet. Water molecules are colored red.