ArticleJournal of the American Chemical Society2014
α-Synuclein-induced membrane remodeling is driven by binding affinity, partition depth, and interleaflet order asymmetry.
Article in Journal of the American Chemical Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 99 citations in OpenAlex.
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- Lipid Composition Drives Mutant Huntingtin Dimerization and Membrane Association: Insights from Computational Simulations.Molecules (Basel, Switzerland) · 2026Article
- The disordered and structured regions ofbioRxiv : the preprint server for biology · 2026Article
- Membrane interfacial potential governs surface condensation and fibrillation of α-Synuclein in neurons.Nature communications · 2026Article
- Sensing the shape of a surface by tightly surface-bound filaments.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Molecular Dynamics Study of α-Synuclein Domain Deletion Mutant Monomers.Biomolecules · 2025Article
- Parkinson disease is a fatty acidopathy.Nature reviews. Neurology · 2025Review
- Exploring the Properties of Curved Lipid Membranes: Comparative Analysis of Atomistic and Coarse-Grained Force Fields.The journal of physical chemistry. B · 2024Article
- The Effects of Lipids on α-Synuclein Aggregation In Vitro.Biomolecules · 2023Review
- α-Synuclein fibril and synaptic vesicle interactions lead to vesicle destruction and increased lipid-associated fibril uptake into iPSC-derived neurons.Communications biology · 2023Article
- Insights into Membrane Curvature Sensing and Membrane Remodeling by Intrinsically Disordered Proteins and Protein Regions.The Journal of membrane biology · 2022Review
- Spiers Memorial Lecture: Analysis andFaraday discussions · 2021Article
- Exploring lipid-dependent conformations of membrane-bound α-synuclein with the VDAC nanopore.Biochimica et biophysica acta. Biomembranes · 2021Article
- Regulation of Mitochondrial Respiration by VDAC Is Enhanced by Membrane-Bound Inhibitors with Disordered Polyanionic C-Terminal Domains.International journal of molecular sciences · 2021Review
- Membrane Interactions of α-Synuclein Revealed by Multiscale Molecular Dynamics Simulations, Markov State Models, and NMR.The journal of physical chemistry. B · 2021Article
- An N-terminal conserved region in human Atg3 couples membrane curvature sensitivity to conjugase activity during autophagy.Nature communications · 2021Article
- In situ kinetic measurements of α-synuclein aggregation reveal large population of short-lived oligomers.PloS one · 2021Article
- Freezing and piercing of in vitro asymmetric plasma membrane by α-synuclein.Communications biology · 2020Article
- How Do Ethanolamine Plasmalogens Contribute to Order and Structure of Neurological Membranes?The journal of physical chemistry. B · 2020Article
- Lipid and Lipid Raft Alteration in Aging and Neurodegenerative Diseases: A Window for the Development of New Biomarkers.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
We have investigated the membrane remodeling capacity of the N-terminal membrane-binding domain of α-synuclein (α-Syn100). Using fluorescence correlation spectroscopy and vesicle clearance assays, we show that α-Syn100 fully tubulates POPG vesicles, the first demonstration that the amphipathic helix on its own is capable of this effect. We also show that at equal density of membrane-bound protein, α-Syn has dramatically reduced affinity for, and does not tubulate, vesicles composed of a 1:1 POPG:POPC mixture. Coarse-grained molecular dynamics simulations suggested that the difference between the pure POPG and mixture results may be attributed to differences in the protein's partition depth, the membrane's hydrophobic thickness, and disruption of acyl chain order. To explore the importance of these attributes compared with the role of the reduced binding energy, we created an α-Syn100 variant in which we removed the hydrophobic core of the non-amyloid component (NAC) domain and tested its impact on pure POPG vesicles. We observed a substantial reduction in binding affinity and tubulation, and simulations of the NAC-null protein suggested that the reduced binding energy increases the protein mobility on the bilayer surface, likely impacting the protein's ability to assemble into organized pretubule structures. We also used simulations to explore a potential role for interleaflet coupling as an additional driving force for tubulation. We conclude that symmetry across the leaflets in the tubulated state maximizes the interaction energy of the two leaflets and relieves the strain induced by the hydrophobic void beneath the amphipathic helix.
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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.