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Earliest events in α-synuclein fibrillation probed with the fluorescence of intrinsic tyrosines

Paper ID Volume ID Publish Year Pages File Format Full-Text
29381 44380 2016 8 PDF Available
Title
Earliest events in α-synuclein fibrillation probed with the fluorescence of intrinsic tyrosines
Abstract

•Intrinsic fluorescence of α-synuclein reports the earliest events of the aggregation.•In the sub-7 ms after acidification, a conformational change occurs in the protein.•4–10 s after acidification, the protein starts to aggregate.

The fluorescence of the four tyrosines of α-synuclein (Syn) was used for probing the earliest events preceding the fibrillation of Syn, during the onset of the so-called lag-time of fibrillation. Steady-state fluorescence experiments revealed an increase in the fluorescence intensity (FI) for Syn solutions at pH values 3 and 2, in comparison with pH 7, and fluorescence decays indicated that the FI increase did not result from suppression of excited-state proton transfer from the tyrosines to aspartates and glutamates, exposure of tyrosines to more hydrophobic environments, or reduction of homo-energy transfer. Instead, the FI increase was due to changes in the population of the tyrosine rotamers at low pH values.Stopped-flow experiments (pH-jumps) showed that the FI enhancement involves two processes: a fast (sub-7 ms) intramolecular (concentration-independent) process, which we assign to the protein collapse at low pH, and a slower intermolecular (concentration-dependent) process of protein dimerization/oligomerization, starting at 4–10 s after acidification.To the best of our knowledge, this is the first work on the experimental detection of these earliest processes in the fibrillation of Syn.

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Keywords
Intrinsic fluorescence probe; pH-jump; Stopped-flow; Protein aggregation
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Earliest events in α-synuclein fibrillation probed with the fluorescence of intrinsic tyrosines
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Photochemistry and Photobiology B: Biology - Volume 154, January 2016, Pages 16–23
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us