ArticleJournal of the American Chemical Society2012
α-Synuclein induces both positive mean curvature and negative Gaussian curvature in membranes.
Article in Journal of the American Chemical Society, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
63 citing papers in PubMed, 113 citations in OpenAlex.
- Differential proteostasis imbalance and the molecular basis of distinct synucleinopathies and tauopathies.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Molecular Dynamics Study of α-Synuclein Domain Deletion Mutant Monomers.Biomolecules · 2025Article
- Tau fibrils induce nanoscale membrane damage and nucleate cytosolic tau at lysosomes.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Interplay of α-synuclein with Lipid Membranes: Cooperative Adsorption, Membrane Remodeling and Coaggregation.JACS Au · 2024Review
- Dissecting membrane interfacial cellular processes: an in vitro reconstitution approach.The European physical journal. Special topics · 2024Review
- 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
- Non-uniform sampling of similar NMR spectra and its application to studies of the interaction between alpha-synuclein and liposomes.Journal of biomolecular NMR · 2023Article
- Amyloids on Membrane Interfaces: Implications for Neurodegeneration.The Journal of membrane biology · 2022Review
- Insights into Membrane Curvature Sensing and Membrane Remodeling by Intrinsically Disordered Proteins and Protein Regions.The Journal of membrane biology · 2022Review
- Article
- Spiers Memorial Lecture: Analysis andFaraday discussions · 2021Article
- Mutations in membrane-fusion subunit of spike glycoprotein play crucial role in the recent outbreak of COVID-19.Journal of medical virology · 2021Article
- Membrane Interactions of α-Synuclein Revealed by Multiscale Molecular Dynamics Simulations, Markov State Models, and NMR.The journal of physical chemistry. B · 2021Article
- Optimizing Gō-MARTINI Coarse-Grained Model for F-BAR Protein on Lipid Membrane.Frontiers in molecular biosciences · 2021Article
- In situ kinetic measurements of α-synuclein aggregation reveal large population of short-lived oligomers.PloS one · 2021Article
- Protein crowding mediates membrane remodeling in upstream ESCRT-induced formation of intraluminal vesicles.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Single-vesicle imaging reveals lipid-selective and stepwise membrane disruption by monomeric α-synuclein.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Deep mutational scanning reveals the structural basis for α-synuclein activity.Nature chemical biology · 2020Article
- Synaptic vesicle mimics affect the aggregation of wild-type and A53T α-synuclein variants differently albeit similar membrane affinity.Protein engineering, design & selection : PEDS · 2019Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Using a combination of X-ray scattering, fluorescence correlation spectroscopy, coarse-grained molecular dynamics (MD) simulations and potential of mean force calculations, we have explored the membrane remodeling effects of monomeric α-synuclein (αS). Our initial findings from multiple approaches are that αS (1) causes a significant thinning of the bilayer and (2) stabilizes positive mean curvature, such that the maximum principle curvature matches that of synaptic vesicles, αS-induced tubules, and the synthetic lipid vesicles to which the protein binds most tightly. This suggests that αS binding to synaptic vesicles likely stabilizes their intrinsic curvature. We then show that αS induces local negative Gaussian curvature, an effect that occurs in regions of αS shown previously via NMR and corroborated by MD simulation to have significant conformational flexibility. The induction of negative Gaussian curvature, which has implications for all curvature-sensing and curvature-generating amphipathic α-helices, supports a hypothesis that connects helix insertion to fusion and fission of vesicles, processes that have recently been linked to αS function. Then, in an effort to explain these biophysical properties of αS, we promote an intrinsic curvature-field model that recasts long-range protein-protein interactions in terms of the interactions between the local curvature fields generated by lipid-protein complexes.
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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.