Human alpha synuclein (αS) has been shown to be N-terminally acetylated in its physiological state. This modification is proposed to modulate αS's function and aggregation into amyloid fibrils. Using bacterially expressed acetylated αS (NTAc-αS) and endogenous αS (Endo-αS) from human erythrocytes, we show that N-terminal acetylation has little impact on αS binding to anionic membranes and thus likely not relevant for regulating membrane affinity. N-terminal acetylation does have an effect on αS aggregation, resulting in a narrower distribution of the aggregation lag times and rates. 2D-IR spectra show that acetylation changes the secondary structure of αS in fibrils. This difference may arise from the slightly higher helical propensity of acetylated αS in solution leading to a more homogenous fibril population with different fibril structure than non-acetylated αS. We speculate that N-terminal acetylation imposes conformational restraints on N-terminal residues in αS, thus predisposing αS towards specific interactions with other binding partners or alternatively decrease nonspecific interactions.

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Journal J. Biol. Chem.
Iyer, A, Roeters, S.J, Schilderink, N, Hommersom, B, Heeren, R.M.A, Woutersen, S, … Subramaniam, V. (2016). The Impact of N-terminal Acetylation of Alpha Synuclein on Phospholipid Membrane Binding and Fibril Structure. J. Biol. Chem., 291, 21110–21122. doi:10.1074%2Fjbc.M116.726612