Stabilization of Partially Folded Conformation During α-synuclein Oligomerization in Both Purified and Cytosolic Preparations

Authors

Vladimir N. Uversky, University of California, Santa CruzFollow
He-Jin Lee, University of California, Santa Cruz
Jie Li, University of California, Santa Cruz
Anthony L. Fink, University of California, Santa Cruz
Seung-Jae Lee, University of California, Santa Cruz

Document Type

Article

Publication Date

2001

Digital Object Identifier (DOI)

https://doi.org/10.1074/jbc.C100551200

Abstract

Aggregation of α-synuclein is tightly associated with many neurodegenerative diseases, such as Parkinson's disease, dementia with Lewy body, Lewy body variant of Alzheimer's disease, multiple system atrophy, and Hallervorden-Spatz disease, implicating a crucial role of aggregated forms of α-synuclein in the pathogenesis. Here, we examined the effect of elevated temperature on the oligomerization and structural changes of α-synuclein in the early stage of aggregation and show that self-assembly is crucial for the stabilization of a partially folded conformation. The efficiency of α-synuclein oligomerization increased proportional to the temperature increase, both in purified form and in crude cytosolic preparation. This oligomerization coincided with a small but reproducible change in the circular dichroism spectrum and an increase in the 1-anilinonaphthalene-8-sulfonic acid binding. The hydrodynamic dimensions of the dimer measured by size exclusion chromatography suggest a pre-molten globule-like structure. These data suggest that partially folded α-synuclein, which is unstable in the monomeric form, is stabilized by self-assembly and that these oligomers may evolve into the fibril nucleus.

Rights Information

This work is licensed under a Creative Commons Attribution 4.0 License.

Was this content written or created while at USF?

No

Citation / Publisher Attribution

Journal of Biological Chemistry, v. 276, issue 47, p. 43495-43498

Scholar Commons Citation

Uversky, Vladimir N.; Lee, He-Jin; Li, Jie; Fink, Anthony L.; and Lee, Seung-Jae, "Stabilization of Partially Folded Conformation During α-synuclein Oligomerization in Both Purified and Cytosolic Preparations" (2001). Molecular Medicine Faculty Publications. 676.
https://digitalcommons.usf.edu/mme_facpub/676