DOI: 10.1073/pnas.0407307101. α-Synuclein structures from fluorescence energy-transfer kinetics: Implications for the role of the protein in Parkinson's disease

α-Synuclein structures from fluorescence energy-transfer kinetics: Implications for the role of the protein in Parkinson's disease

10.1073/pnas.0407307101

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Parkinson's disease is associated with the deposition and accumulation of α-synuclein fibrils in the brain. A30P and A53T mutations have been linked to the early-onset familial disease state. Time-resolved tryptophan fluorescence energy-transfer measurements have been used to probe the structures of pseudo-wild-type and mutant (A30P) α-synucleins at physiological pH (7.4), in acidic pH (4.4) solutions, and in the presence of SDS micelles, a membrane mimic. Fluorescent donor–energy acceptor (DA) distance distributions for six different tryptophan/3-nitro-tyrosine pairs reveal the presence of compact, intermediate, and extended conformations of the protein. CD spectra indicate that the protein develops substantial helical structure in the presence of SDS micelles. DA distributions show that micelles induce compaction in the N-terminal region and expansion of the acidic C terminus. In acidic solutions, there is an increased population of collapsed structures in the C-terminal region. Energy-transfer measurements demonstrate that the average DA distances for the W4–Y19 and Y19–W39 pairs are longer in one of the two disease-related mutants (A30P).

Bibliography

Lee, J. C., Langen, R., Hummel, P. A., Gray, H. B., & Winkler, J. R. (2004). Î±-Synuclein structures from fluorescence energy-transfer kinetics: Implications for the role of the protein in Parkinsonâs disease. Proceedings of the National Academy of Sciences, 101(47), 16466â16471.

Authors 5

Jennifer C. Lee (first)
Ralf Langen (additional)
Patrick A. Hummel (additional)
Harry B. Gray (additional)
Jay R. Winkler (additional)

References 65 Referenced 131

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Dates

Type	When
Created	20 years, 9 months ago (Nov. 9, 2004, 9:58 p.m.)
Deposited	1 year, 7 months ago (Jan. 15, 2024, 12:34 a.m.)
Indexed	1 month ago (July 24, 2025, 8:05 a.m.)
Issued	20 years, 9 months ago (Nov. 9, 2004)
Published	20 years, 9 months ago (Nov. 9, 2004)
Published Online	20 years, 9 months ago (Nov. 9, 2004)
Published Print	20 years, 9 months ago (Nov. 23, 2004)

Funders 0

None

BibTeX

@article{Lee_2004, title={α-Synuclein structures from fluorescence energy-transfer kinetics: Implications for the role of the protein in Parkinson’s disease}, volume={101}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0407307101}, DOI={10.1073/pnas.0407307101}, number={47}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Lee, Jennifer C. and Langen, Ralf and Hummel, Patrick A. and Gray, Harry B. and Winkler, Jay R.}, year={2004}, month=nov, pages={16466–16471} }

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