The Impact of N-terminal Acetylation of alpha-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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Human alpha-synuclein (alpha S) has been shown to be N terminally acetylated in its physiological state. This modification is proposed to modulate the function and aggregation of alpha S into amyloid fibrils. Using bacterially expressed acetylated-alpha S (NTAc-alpha S) and endogenous alpha S (Endo-alpha S) from human erythrocytes, we show that N-terminal acetylation has little impact on alpha S binding to anionic membranes and thus likely not relevant for regulating membrane affinity. N-terminal acetylation does have an effect on alpha S aggregation, resulting in a narrower distribution of the aggregation lag times and rates. 2D-IR spectra show that acetylation changes the secondary structure of alpha S in fibrils. This difference may arise from the slightly higher helical propensity of acetylated-alpha S in solution leading to a more homogenous fibril population with different fibril structure than non-acetylated alpha S. We speculate that N-terminal acetylation imposes conformational restraints on N-terminal residues in alpha S, thus predisposing alpha S toward specific interactions with other binding partners or alternatively decrease nonspecific interactions.
Original languageEnglish
Pages (from-to)21110-21122
JournalJournal of Biological Chemistry
Issue number40
Publication statusPublished - 30 Sep 2016

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