Extended Data Fig. 9: MSA filaments differ from those assembled with recombinant α-synuclein.

a, Overlay of the three-layered L-shaped motifs of MSA α-synuclein filaments (yellow, orange, pink and purple) and filaments assembled in vitro using recombinant α-synuclein that contain a similar motif (grey). Despite topological similarities, none of the three-layered L-shaped motifs in recombinant α-synuclein protofilaments is identical to those of MSA protofilaments. The closest similarity to an in vitro structure is between PF-IIB₂ and PDB 6PEO⁵², which differ only in the bend positions in the outer layer (between E57 and K58 for PF-IIB₂ and between T59 and K60 for PDB 6PEO). b, Overlay of MSA and recombinant α-synuclein structures on the basis of the turn at residues K43–V52, revealing a conserved interface between residues E46–V49 and V74–A78 or A76–K80 (red highlight), including the formation of a salt bridge between E46 and K80. c, Overlay of MSA and recombinant α-synuclein structures on the basis of the conserved turn at residues V63–T72, revealing a second conserved turn (V63–T72) and a conserved packing through tight interdigitations of small side chains between residues A69–T72 and residues on the inner layer (green highlight). In MSA PF-IA and PF-IIA filaments, as well as in PDB 6OSM⁴⁷, these residues are A89 and A91; in MSA PF-IB and PF-IIB filaments, as well as in PDB 6PEO, they are G93 and V95; in several recombinant α-synuclein structures, they are A91 and G93.