ArticleJournal of molecular biology2007
Relationships between the sequence of alpha-synuclein and its membrane affinity, fibrillization propensity, and yeast toxicity.
Article in Journal of molecular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.
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Who cites it
108 citing papers in PubMed, 248 citations in OpenAlex.
- From Glycation to Toxicity: α-Synuclein Oligomers, Oxidative Stress, and Multi-Targeted Protection by Trans-Ferulic Acid.Cell biochemistry and biophysics · 2026Article
- Unraveling Luteolin's Modulatory Effects on α-Synuclein Aggregation: A Combined Biophysical, Computational, and C. elegans Approach.Cell biochemistry and biophysics · 2026Article
- Quantifying the Acute Toxicity of Alpha-Synuclein Membrane-Accumulation in a Cell-Based Assay.Journal of molecular neuroscience : MN · 2026Article
- A Rigid Supramolecular Solution to a Flexible Problem: A Multifunctional Calix[4]arene-Based Strategy to Prevent α‑Synuclein Toxicity.ACS central science · 2026Article
- Stress-specific expression of HSPA and DNAJ chaperones regulated by NRF2/HSF1 in neurodegenerative conditions.Molecular and cellular biochemistry · 2026Article
- Changes in the concentration of phosphatidylcholine in lipid bilayers determines the aggregation rate of transthyretin.Biophysical chemistry · 2026Article
- Familial mutations modulate α-synuclein interactions with key neuronal membrane lipids.The FEBS journal · 2026Article
- Quantifying the Acute Toxicity of Alpha-Synuclein Membrane-Accumulation in a Cell-Based Assay.Research square · 2026Article
- Intestinal inflammation promotes neuroinflammation and PD-associated nigrostriatal pathology independently of LRRK2 G2019S kinase activity.Frontiers in cellular neuroscience · 2026Article
- The Yeast Parkinson's Disease Model Exhibits An Increase in Peroxisome Number Independent of the Division Proteins Vps1 and Dnm1.Molecular neurobiology · 2025Article
- Article
- Multivalent interaction induces phase separation and formation of more toxic aggregates of α-syn in a yeast model of Parkinson's disease.Protein science : a publication of the Protein Society · 2025Article
- Solid-state NMR assignment of α-synuclein polymorph prepared from helical intermediate.Biomolecular NMR assignments · 2024Article
- Interactions of alpha-synuclein with membranes in Parkinson's disease: Mechanisms and therapeutic strategies.Neurobiology of disease · 2024Review
- Length and saturation of choline plasmalogens alter the aggregation rate of α-synuclein but not the toxicity of amyloid fibrils.International journal of biological macromolecules · 2024Article
- Molecular Behavior of α-Synuclein Is Associated with Membrane Transport, Lipid Metabolism, and Ubiquitin-Proteasome Pathways in Lewy Body Disease.International journal of molecular sciences · 2024Article
- Cell membrane proteome analysis in HEK293T cells challenged with α-synuclein amyloids.Journal of biosciences · 2024Article
- Adding hydrophobicity or positive charges to the cytosolic half of the α-synuclein 3-11 helix increases membrane association and S129 phosphorylation.FEBS letters · 2024Article
- Specific detection of protein carbonylation sites by 473 nm photodissociation mass spectrometry.Analytical and bioanalytical chemistry · 2023Article
- Saturation of fatty acids in phosphatidic acid uniquely alters transthyretin stability changing morphology and toxicity of amyloid fibrils.Chemistry and physics of lipids · 2023Article
48 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
To investigate the alpha-synuclein protein and its role in Parkinson's disease, we screened a library of random point mutants both in vitro and in yeast to find variants in an unbiased way that could help us understand the sequence-phenotype relationship. We developed a rapid purification method that allowed us to screen 59 synuclein mutants in vitro and discovered two double-point mutants that fibrillized slowly relative to wild-type, A30P, and A53T alpha-synucleins. The yeast toxicity of all of these proteins was measured, and we found no correlation with fibrillization rate, suggesting that fibrillization is not necessary for synuclein-induced yeast toxicity. We found that beta-synuclein was of intermediate toxicity to yeast, and gamma-synuclein was non-toxic. Co-expression of Parkinson's disease-related genes DJ-1, parkin, Pink1, UCH-L1, or synphilin, with synuclein, did not affect synuclein toxicity. A second screen, of several thousand library clones in yeast, identified 25 non-toxic alpha-synuclein sequence variants. Most of these contained a mutation to either proline or glutamic acid that caused a defect in membrane binding. We hypothesize that yeast toxicity is caused by synuclein binding directly to membranes at levels sufficient to non-specifically disrupt homeostasis.
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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.