ArticleThe Journal of biological chemistry2015
Familial Parkinson disease-associated mutations alter the site-specific microenvironment and dynamics of α-synuclein.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 49 citations in OpenAlex.
- Protocol for using an ELISA to detect total α-synuclein levels in Drosophila melanogaster lines expressing human α-synuclein point mutations.STAR protocols · 2026Article
- Protocol for using an ELISA to detect total α-synuclein levels inbioRxiv : the preprint server for biology · 2026Article
- Exploring the Impact of Physiological C-Terminal Truncation on α-Synuclein Conformations to Unveil Mechanisms Regulating Pathological Aggregation.Journal of chemical information and modeling · 2024Article
- Early-Onset Parkinson Mutation Remodels Monomer-Fibril Interactions to Allosterically Amplify Synuclein's Amyloid Cascade.JACS Au · 2023Article
- Effects of Mutations and Post-Translational Modifications on α-Synuclein In Vitro Aggregation.Journal of molecular biology · 2022Review
- Molecular Insights into the Misfolding and Dimerization Dynamics of the Full-Length α-Synuclein from Atomistic Discrete Molecular Dynamics Simulations.ACS chemical neuroscience · 2022Article
- Article
- Mitochondrial dysfunction is a key pathological driver of early stage Parkinson's.Acta neuropathologica communications · 2022Article
- Structural and Functional Insights into α-Synuclein Fibril Polymorphism.Biomolecules · 2021Review
- Impact of Fatty Acid-Binding Proteins in α-Synuclein-Induced Mitochondrial Injury in Synucleinopathy.Biomedicines · 2021Review
- α-Synuclein aggregation nucleates through liquid-liquid phase separation.Nature chemistry · 2020Article
- Diverse Structural Conversion and Aggregation Pathways of Alzheimer's Amyloid-β (1-40).ACS nano · 2019Article
- Lipids asFrontiers in neuroscience · 2019Review
- The Non-amyloidal Component Region of α-Synuclein Is Important for α-Synuclein Transport Within Axons.Frontiers in cellular neuroscience · 2019Article
- Fluorescence spectroscopy for revealing mechanisms in biology: Strengths and pitfalls.Journal of biosciences · 2018Review
- Unveiling a Selective Mechanism for the Inhibition of α-Synuclein Aggregation by β-Synuclein.International journal of molecular sciences · 2018Article
- Looking at the recent advances in understanding α-synuclein and its aggregation through the proteoform prism.F1000Research · 2017Review
- Effect of curcumin analogs onα-synuclein aggregation and cytotoxicity.Scientific reports · 2016Article
- Alpha-Synuclein Proteins Promote Pro-Inflammatory Cascades in Microglia: Stronger Effects of the A53T Mutant.PloS one · 2016Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human α-synuclein (α-Syn) is a natively unstructured protein whose aggregation into amyloid fibrils is associated with Parkinson disease (PD) pathogenesis. Mutations of α-Syn, E46K, A53T, and A30P, have been linked to the familial form of PD. In vitro aggregation studies suggest that increased propensity to form non-fibrillar oligomers is the shared property of these familial PD-associated mutants. However, the structural basis of the altered aggregation propensities of these PD-associated mutants is not yet clear. To understand this, we studied the site-specific structural dynamics of wild type (WT) α-Syn and its three PD mutants (A53T, E46K, and A30P). Tryptophan (Trp) was substituted at the N terminus, central hydrophobic region, and C terminus of all α-Syns. Using various biophysical techniques including time-resolved fluorescence studies, we show that irrespective of similar secondary structure and early oligomerization propensities, familial PD-associated mutations alter the site-specific microenvironment, solvent exposure, and conformational flexibility of the protein. Our results further show that the common structural feature of the three PD-associated mutants is more compact and rigid sites at their N and C termini compared with WT α-Syn that may facilitate the formation of a partially folded intermediate that eventually leads to their increased oligomerization propensities.
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