Extended Data Fig. 6: The inter-protofilament interfaces of MSA type I and type II α-synuclein filaments.
From: Structures of α-synuclein filaments from multiple system atrophy
a, b, Rendered view of secondary structure elements in MSA type I (a) and type II (b) protofilament folds perpendicular to the helical axis of inter-protofilament interfaces, depicted as three rungs. Because of variations in the height of both polypeptide chains along the helical axis, each α-synuclein molecule interacts with three different molecules in the opposing protofilament. If one considers the interaction between two opposing molecules to be on the same β-sheet rung in the central cavity, the N-terminal arm of PF-IA or PF-IIA interacts with the C-terminal body of the PF-IB or PF-IIB molecule, which is one rung higher, while the C-terminal body of PF-IA or PF-IIA interacts with the N-terminal arm of the PF-IB or PF-IIB molecule, which is one rung lower. c, d, Compatibility of mutant α-synuclein (G51D and A53E) with MSA type I and type II filaments. Close-up views of atomic models of type I (c) and type II (d) α-synuclein folds containing D51 (cyan) and E53 (green). Each mutation adds two negatively charged side chains per rung in the second shell of residues around the central cavity, thus reducing the net positive charge of the shell.
