Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published November 23, 2004 | Published
Journal Article Open

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

Abstract

Parkinson's disease is associated with the deposition and accumulation of alpha-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) alpha-synucleins at physiological pH (7.4), in acidic pH (4.4) solutions, and in the presence of SIDS 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. CID spectra indicate that the protein develops substantial helical structure in the presence of SIDS 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).

Additional Information

© 2004 by the National Academy of Sciences. Contributed by Harry B. Gray, October 4, 2004. This work was supported by the Parkinson's Disease Foundation (J.R.W.), the National Parkinson Foundation (J.R.W.), the Beckman Macular Research Center (H.B.G. and R.L.), and the Arnold and Mabel Beckman Foundation (H.B.G. and J.R.W.), National Institutes of Health Grants GM068461 (to J.R.W.) and P50 AG05142 (to R.L.), and Department of Energy Grant DE-FG02-02ER15359 (to J.R.W.). J.C.L. thanks the Arnold and Mabel Beckman Foundation for a Beckman Senior Research Fellowship.

Attached Files

Published - LEEpnas04.pdf

Files

LEEpnas04.pdf
Files (576.6 kB)
Name Size Download all
md5:91f9e7e03a9ac54bbcf8deedcf03f9d3
576.6 kB Preview Download

Additional details

Created:
August 22, 2023
Modified:
October 13, 2023