ArticlePloS one2014
N-alpha-acetylation of α-synuclein increases its helical folding propensity, GM1 binding specificity and resistance to aggregation.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed, 163 citations in OpenAlex.
- N-Terminal Amine Chemistry Influences α-Synuclein Interactions with Lipid Bilayers.Biochemistry · 2026Article
- Impact of N-terminal acetylation on Cu(I) coordination by alpha synuclein protein.Journal of inorganic biochemistry · 2026Article
- The Involvement of Ceramide, Sphingosine-1-Phosphate and Ganglioside GM1 in Regulating Some Nervous System Functions.International journal of molecular sciences · 2025Review
- Aggregation-prone alpha-synuclein proteoforms and dysregulated molecular signatures in the vermiform appendix of synucleinopathy patients.bioRxiv : the preprint server for biology · 2025Article
- Acute introduction of monomeric or multimeric α-synuclein induces distinct impacts on synaptic vesicle trafficking at lamprey giant synapses.The Journal of physiology · 2025Article
- Myelin Lipid Alterations in Neurodegenerative Diseases: Landscape and Pathogenic Implications.Antioxidants & redox signaling · 2024Review
- Folding of N-terminally acetylated α-synuclein upon interaction with lipid membranes.Biophysical journal · 2024Article
- Posttranslational Modifications ofPharmacological reviews · 2024Review
- Longitudinal adaptive behavioral outcomes in Ogden syndrome by seizure status and therapeutic intervention.American journal of medical genetics. Part A · 2024Article
- Alpha-Synuclein and GM1 Ganglioside Co-Localize in Neuronal Cytosol Leading to Inverse Interaction-Relevance to Parkinson's Disease.International journal of molecular sciences · 2024Article
- Longitudinal Adaptive Behavioral Outcomes in Ogden Syndrome by Seizure Status and Therapeutic Intervention.medRxiv : the preprint server for health sciences · 2024Article
- Gangliosides as Therapeutic Targets for Neurodegenerative Diseases.Journal of lipids · 2024Review
- GM1 ganglioside exerts protective effects against glutamate-excitotoxicity via its oligosaccharide in wild-type and amyotrophic lateral sclerosis motor neurons.FEBS open bio · 2023Article
- The Effects of Lipids on α-Synuclein Aggregation In Vitro.Biomolecules · 2023Review
- GM1 oligosaccharide efficacy against α-synuclein aggregation and toxicity in vitro.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2023Article
- The relationship between depletion of brain GM1 ganglioside and Parkinson's disease.FEBS open bio · 2023Review
- Changes in α-Synuclein Posttranslational Modifications in an AAV-Based Mouse Model of Parkinson's Disease.International journal of molecular sciences · 2023Article
- Loss of N-terminal acetyltransferase A activity induces thermally unstable ribosomal proteins and increases their turnover in Saccharomyces cerevisiae.Nature communications · 2023Article
- Ganglioside GM1 and the Central Nervous System.International journal of molecular sciences · 2023Review
- GM1 Ganglioside as a Disease-Modifying Therapeutic for Parkinson's Disease: A Multi-Functional Glycosphingolipid That Targets Multiple Parkinson's Disease-Relevant Pathogenic Mechanisms.International journal of molecular sciences · 2023Review
32 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
A switch in the conformational properties of α-synuclein (αS) is hypothesized to be a key step in the pathogenic mechanism of Parkinson's disease (PD). Whereas the beta-sheet-rich state of αS has long been associated with its pathological aggregation in PD, a partially alpha-helical state was found to be related to physiological lipid binding; this suggests a potential role of the alpha-helical state in controlling synaptic vesicle cycling and resistance to β-sheet rich aggregation. N-terminal acetylation is the predominant post-translational modification of mammalian αS. Using circular dichroism, isothermal titration calorimetry, and fluorescence spectroscopy, we have analyzed the effects of N-terminal acetylation on the propensity of recombinant human αS to form the two conformational states in interaction with lipid membranes. Small unilamellar vesicles of negatively charged lipids served as model membranes. Consistent with previous NMR studies using phosphatidylserine, we found that membrane-induced α-helical folding was enhanced by N-terminal acetylation and that greater exothermic heat could be measured upon vesicle binding of the modified protein. Interestingly, the folding and lipid binding enhancements with phosphatidylserine in vitro were weak when compared to that of αS with GM1, a lipid enriched in presynaptic membranes. The resultant increase in helical folding propensity of N-acetylated αS enhanced its resistance to aggregation. Our findings demonstrate the significance of the extreme N-terminus for folding nucleation, for relative GM1 specificity of αS-membrane interaction, and for a protective function of N-terminal-acetylation against αS aggregation mediated by GM1.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.