ArticleProceedings of the National Academy of Sciences of the United States of America2012
Aggregation of α-synuclein is kinetically controlled by intramolecular diffusion.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed.
- Single-fibril Förster resonance energy transfer imaging and deep learning reveal concentration dependence of amyloid β 42 aggregation pathways.PNAS nexus · 2025Article
- The role of biomolecular condensates in protein aggregation.Nature reviews. Chemistry · 2024Review
- O-GlcNAc Modification of α-Synuclein Can Alter Monomer Dynamics to Control Aggregation Kinetics.ACS chemical neuroscience · 2024Article
- Molecular Tweezers: Supramolecular Hosts with Broad-Spectrum Biological Applications.Pharmacological reviews · 2023Review
- Decreased Water Mobility Contributes To Increased α-Synuclein Aggregation.Angewandte Chemie (International ed. in English) · 2023Article
- Decreased Water Mobility Contributes To Increased α-Synuclein Aggregation.Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2023Article
- Thermodynamics and kinetics of the amyloid-β peptide revealed by Markov state models based on MD data in agreement with experiment.Chemical science · 2021Article
- Zinc determines dynamical properties and aggregation kinetics of human insulin.Biophysical journal · 2021Article
- "Janus-Faced" α-Synuclein: Role in Parkinson's Disease.Frontiers in cell and developmental biology · 2021Review
- Identification of Two Novel Peptides That Inhibit α-Synuclein Toxicity and Aggregation.Frontiers in molecular neuroscience · 2021Article
- Roles, Characteristics, and Analysis of Intrinsically Disordered Proteins: A Minireview.Life (Basel, Switzerland) · 2020Review
- N-Terminal Decarboxylation as a Probe for Intramolecular Contact Formation in γ-Glu-(Pro)The journal of physical chemistry. B · 2020Article
- Heterogeneous folding and stretched kinetics.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Reorientational Dynamics of Amyloid-β from NMR Spin Relaxation and Molecular Simulation.The journal of physical chemistry letters · 2019Article
- Intramolecular Diffusion in α-Synuclein: It Depends on How You Measure It.Biophysical journal · 2018Article
- Exploring the role of post-translational modifications in regulating α-synuclein interactions by studying the effects of phosphorylation on nanobody binding.Protein science : a publication of the Protein Society · 2018Article
- Femtosecond Hydration Map of Intrinsically Disordered α-Synuclein.Biophysical journal · 2018Article
- Pre-aggregation kinetics and intermediates of α-synuclein monitored by the ESIPT probe 7MFE.European biophysics journal : EBJ · 2018Article
- Alpha-synuclein, Proteotoxicity and Parkinson's Disease: Search for Neuroprotective Therapy.Current neuropharmacology · 2018Review
- A Focus on the Beneficial Effects of Alpha Synuclein and a Re-Appraisal of Synucleinopathies.Current protein & peptide science · 2018Review
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We hypothesize that the first step of aggregation of disordered proteins, such as α-synuclein, is controlled by the rate of backbone reconfiguration. When reconfiguration is fast, bimolecular association is not stable, but as reconfiguration slows, association is more stable and subsequent aggregation is faster. To investigate this hypothesis, we have measured the rate of intramolecular diffusion in α-synuclein, a protein involved in Parkinson's disease, under solvent conditions that accelerate or decelerate aggregation. Using the method of tryptophan-cysteine (Trp-Cys) quenching, the rate of intramolecular contact is measured in four different loops along the chain length. This intrinsically disordered protein is highly diffusive at low temperature at neutral pH, when aggregation is slow, and compacts and diffuses more slowly at high temperature or low pH, when aggregation is rapid. Diffusion also slows with the disease mutation A30P. This work provides unique insights into the earliest steps of α-synuclein aggregation pathway and should provide the basis for the development of drugs that can prevent aggregation at the initial stage.
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