The impact of N-terminal acetylation of αS-synuclein on phospholipid membrane binding and fibril structure

Aditya Iyer, Steven J. Roeters, Nathalie Schilderink, Bob Hommersom, Ron M A Heeren, Sander Woutersen, Mireille M A E Claessens, Vinod Subramaniam

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Human alpha synuclein (S) has been shown to be N-terminally acetylated in its physiological state. This modification is proposed to modulate S's function and aggregation into amyloid fibrils. Using bacterially expressed acetylated αS (NTAc-S) and endogenous S (Endo-S) from human erythrocytes, we show that N-terminal acetylation has little impact on S 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 S in fibrils. This difference may arise from the slightly higher helical propensity of acetylated S 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 S, thus predisposing S towards specific interactions with other binding partners or alternatively decrease nonspecific interactions.
Original languageEnglish
Pages (from-to)21110-21122
Number of pages13
JournalThe Journal of Biological Chemistry
Issue number40
Publication statusPublished - 30-Sept-2016
Externally publishedYes

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