title: The Impact of N-terminal Acetylation of α-Synuclein on Phospholipid Membrane Binding and Fibril Structure.
abstract: Human α-synuclein (αS) has been shown to be N terminally acetylated in its physiological state. This modification is proposed to modulate the function and aggregation of αS 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 toward specific interactions with other binding partners or alternatively decrease nonspecific interactions.
authors.affiliation: From the Nanoscale Biophysics Group, FOM Institute AMOLF, Amsterdam, the Nanobiophysics Group, MESA+ Institute for Nanotechnology, University of Twente, Enschede.
authors.forename: Aditya
authors.initials: A
authors.lastname: Iyer
authors.affiliation: the Van't Hoff Institute for Molecular Sciences, University of Amsterdam, Amsterdam.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Roeters
authors.affiliation: the Nanobiophysics Group, MESA+ Institute for Nanotechnology, University of Twente, Enschede.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Schilderink
authors.affiliation: the BioImaging MS Group, FOM Institute AMOLF, Amsterdam, The Netherlands.
authors.forename: Bob
authors.initials: B
authors.lastname: Hommersom
authors.affiliation: the BioImaging MS Group, FOM Institute AMOLF, Amsterdam, The Netherlands, the M4I, The Maastricht MultiModal Molecular Imaging Institute, University of Maastricht, and.
authors.forename: Ron M A
authors.initials: RM
authors.lastname: Heeren
authors.affiliation: the Van't Hoff Institute for Molecular Sciences, University of Amsterdam, Amsterdam, s.woutersen@uva.nl.
authors.forename: Sander
authors.initials: S
authors.lastname: Woutersen
authors.affiliation: the Nanobiophysics Group, MESA+ Institute for Nanotechnology, University of Twente, Enschede, m.m.a.e.claessens@utwente.nl.
authors.forename: Mireille M A E
authors.initials: MM
authors.lastname: Claessens
authors.affiliation: From the Nanoscale Biophysics Group, FOM Institute AMOLF, Amsterdam, the Nanobiophysics Group, MESA+ Institute for Nanotechnology, University of Twente, Enschede, the Vrije Universiteit Amsterdam, De Boelelaan 1105, 1081 HV Amsterdam, The Netherlands v.subramaniam@vu.nl.
authors.forename: Vinod
authors.identifier: http://orcid.org/0000-0001-6712-7266
authors.initials: V
authors.lastname: Subramaniam
mesh_terms: D000107:Acetylation; D006801:Humans; D008567:Membranes, Artificial; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism; D066329:Protein Aggregates; D013055:Spectrophotometry, Infrared; D051844:alpha-Synuclein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D008567:Membranes, Artificial; D010743:Phospholipids; D066329:Protein Aggregates; C497604:SNCA protein, human; D051844:alpha-Synuclein
keywords: amyloid; circular dichroism (CD); lipid-protein interaction; post-translational modification (PTM); protein conformation; protein self-assembly