ArticleBiophysical journal2015
Direct Detection of α-Synuclein Dimerization Dynamics: Single-Molecule Fluorescence Analysis.
Article in Biophysical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Microfluidic platform for understanding Parkinson's disease and α-synuclein conformation.Translational neurodegeneration · 2025Review
- Exploration of Resveratrol as a Potent Modulator of α-Synuclein Fibril Formation.ACS chemical neuroscience · 2024Article
- Assembly of Synaptic Protein-DNA Complexes: Critical Role of Non-Specific Interactions.International journal of molecular sciences · 2023Article
- Structural and dynamic insights into α-synuclein dimer conformations.Structure (London, England : 1993) · 2023Article
- Aggregation of Disordered Proteins Associated with Neurodegeneration.International journal of molecular sciences · 2023Review
- Wild-TypeFrontiers in molecular biosciences · 2022Article
- Implementing Complementary Approaches to Shape the Mechanism of α-Synuclein Oligomerization as a Model of Amyloid Aggregation.Molecules (Basel, Switzerland) · 2021Review
- Monitoring alpha-synuclein oligomerization and aggregation using bimolecular fluorescence complementation assays: What you see is not always what you get.Journal of neurochemistry · 2021Article
- Alpha-Synuclein Aggregation in Parkinson's Disease.Frontiers in medicine · 2021Review
- Mechanical Stability of a Small, Highly-Luminescent Engineered Protein NanoLuc.International journal of molecular sciences · 2020Article
- Review
- Intrinsically Disordered Regions of the DNA-Binding Domain of Human FoxP1 Facilitate Domain Swapping.Journal of molecular biology · 2020Article
- High-Speed Atomic Force Microscopy Reveals the Structural Dynamics of the Amyloid-β and Amylin Aggregation Pathways.International journal of molecular sciences · 2020Review
- AFM Probing of Amyloid-Beta 42 Dimers and Trimers.Frontiers in molecular biosciences · 2020Article
- Spontaneous self-assembly of amyloid β (1-40) into dimers.Nanoscale advances · 2019Article
- Probing the Basis of α-Synuclein Aggregation by Comparing Simulations to Single-Molecule Experiments.Biophysical journal · 2019Article
- Assembly of α-synuclein aggregates on phospholipid bilayers.Biochimica et biophysica acta. Proteins and proteomics · 2019Article
- Force clamp approach for characterization of nano-assembly in amyloid beta 42 dimer.Nanoscale · 2019Article
- α-Synuclein-Confocal Nanoscanning (ASYN-CONA), a Bead-Based Assay for Detecting Early-Stage α-Synuclein Aggregation.Analytical chemistry · 2019Article
- The Non-amyloidal Component Region of α-Synuclein Is Important for α-Synuclein Transport Within Axons.Frontiers in cellular neuroscience · 2019Article
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7 authors.
Funding
Abstract
The aggregation of α-synuclein (α-Syn) is linked to Parkinson's disease. The mechanism of early aggregation steps and the effect of pathogenic single-point mutations remain elusive. We report here a single-molecule fluorescence study of α-Syn dimerization and the effect of mutations. Specific interactions between tethered fluorophore-free α-Syn monomers on a substrate and fluorophore-labeled monomers diffusing freely in solution were observed using total internal reflection fluorescence microscopy. The results showed that wild-type (WT) α-Syn dimers adopt two types of dimers. The lifetimes of type 1 and type 2 dimers were determined to be 197 ± 3 ms and 3334 ± 145 ms, respectively. All three of the mutations used, A30P, E46K, and A53T, increased the lifetime of type 1 dimer and enhanced the relative population of type 2 dimer, with type 1 dimer constituting the major fraction. The kinetic stability of type 1 dimers (expressed in terms of lifetime) followed the order A30P (693 ± 14 ms) > E46K (292 ± 5 ms) > A53T (226 ± 6 ms) > WT (197 ± 3 ms). Type 2 dimers, which are more stable, had lifetimes in the range of several seconds. The strongest effect, observed for the A30P mutant, resulted in a lifetime 3.5 times higher than observed for the WT type 1 dimer. This mutation also doubled the relative fraction of type 2 dimer. These data show that single-point mutations promote dimerization, and they suggest that the structural heterogeneity of α-Syn dimers could lead to different aggregation pathways.
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