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The Impact of N-terminal Acetylation of α-Synuclein on Phospholipid Membrane Binding and Fibril Structure
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,...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Society for Biochemistry and Molecular Biology
2016
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5076520/ https://www.ncbi.nlm.nih.gov/pubmed/27531743 http://dx.doi.org/10.1074/jbc.M116.726612 |
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author | Iyer, Aditya Roeters, Steven J. Schilderink, Nathalie Hommersom, Bob Heeren, Ron M. A. Woutersen, Sander Claessens, Mireille M. A. E. Subramaniam, Vinod |
author_facet | Iyer, Aditya Roeters, Steven J. Schilderink, Nathalie Hommersom, Bob Heeren, Ron M. A. Woutersen, Sander Claessens, Mireille M. A. E. Subramaniam, Vinod |
author_sort | Iyer, Aditya |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5076520 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-50765202016-10-25 The Impact of N-terminal Acetylation of α-Synuclein on Phospholipid Membrane Binding and Fibril Structure Iyer, Aditya Roeters, Steven J. Schilderink, Nathalie Hommersom, Bob Heeren, Ron M. A. Woutersen, Sander Claessens, Mireille M. A. E. Subramaniam, Vinod J Biol Chem Molecular Biophysics 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. American Society for Biochemistry and Molecular Biology 2016-09-30 2016-08-16 /pmc/articles/PMC5076520/ /pubmed/27531743 http://dx.doi.org/10.1074/jbc.M116.726612 Text en © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version free via Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0) . |
spellingShingle | Molecular Biophysics Iyer, Aditya Roeters, Steven J. Schilderink, Nathalie Hommersom, Bob Heeren, Ron M. A. Woutersen, Sander Claessens, Mireille M. A. E. Subramaniam, Vinod The Impact of N-terminal Acetylation of α-Synuclein on Phospholipid Membrane Binding and Fibril Structure |
title | The Impact of N-terminal Acetylation of α-Synuclein on Phospholipid Membrane Binding and Fibril Structure |
title_full | The Impact of N-terminal Acetylation of α-Synuclein on Phospholipid Membrane Binding and Fibril Structure |
title_fullStr | The Impact of N-terminal Acetylation of α-Synuclein on Phospholipid Membrane Binding and Fibril Structure |
title_full_unstemmed | The Impact of N-terminal Acetylation of α-Synuclein on Phospholipid Membrane Binding and Fibril Structure |
title_short | The Impact of N-terminal Acetylation of α-Synuclein on Phospholipid Membrane Binding and Fibril Structure |
title_sort | impact of n-terminal acetylation of α-synuclein on phospholipid membrane binding and fibril structure |
topic | Molecular Biophysics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5076520/ https://www.ncbi.nlm.nih.gov/pubmed/27531743 http://dx.doi.org/10.1074/jbc.M116.726612 |
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