Fig. 4: Comparison of the structures of apo SOD1 dimer and SOD1 fibril.

a Sequence alignment of the full-length apo human SOD1 (1 to 153) monomer with eight β-strands colored violet (β1’), blue (β2’), light blue (β3’), light cyan (β4’), light green (β5’), yellow (β6’), pink (β7’), and light magenta (β8’), two α-helices colored gray (α1) and magenta (α2), and a single disulfide bond between Cys⁵⁷ in α1 and Cys¹⁴⁶ in β8’ in each subunit¹⁰. Sequence alignment of the SOD1 fibril core comprising residues 3–55 and 86–153 from full-length human SOD1 (1 to 153) with the observed thirteen β strands colored violet (β1), blue (β2), light blue (β3), cyan (β4), light cyan (β5), green (β6), light green (β7), yellow (β8), gold (β9), orange (β10), pink (β11), magenta (β12), and light magenta (β13). Dashed boxes correspond to residues 1–2 and residues 56–85, which were not modeled in the cryo-EM density. Among two hundred and sixteen mutations linked to familial ALS^{1,2,3,4,5,8,17,18,19,20,21,22,25,26,29,44,45,46,47,48,49,50} (https://alsod.iop.kcl.ac.uk/), one hundred and eighty-two clinically identified mutations are located within the SOD1 fibril core structure, in which one hundred and five representative genetic ALS-related mutations are listed in a. Orange, salt bridge mutations; green, hydrogen bond mutations. b Ribbon representation of the structure of full-length apo human SOD1 (1–153) dimer with eight β-strands (to form a β-barrel), two α-helices, and a disulfide bridge (yellow line) linking α1 and β8’ in each subunit (PDB 1HL4)¹⁰. c Ribbon representation of the structure of an SOD1 fibril core containing one molecular layer and thirteen β-strands, in which the N-terminal segment contains six β strands (β1–β6) and the C-terminal segment contains seven β strands (β7–β13).