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Stabilization of Partially Folded Conformation during alpha-Synuclein Oligomerization in Both Purified and Cytosolic Preparationsстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Uversky Vladimir N., Lee He-Jin, Li Jie, Fink Anthony L., Lee Seung-Jae
- Журнал: Journal of Biological Chemistry
- Том: 276
- Номер: 47
- Год издания: 2001
- Издательство: American Society for Biochemistry and Molecular Biology Inc.
- Местоположение издательства: United States
- Первая страница: 43495
- Последняя страница: 43498
- DOI: 10.1074/jbc.c100551200
- Аннотация: Aggregation of alpha-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 alpha-synuclein in the pathogenesis. Here, we examined the effect of elevated temperature on the oligomerization and structural changes of alpha-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 alpha-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 alpha-synuclein, which is unstable in the monomeric form, is stabilized by self-assembly and that these oligomers may evolve into the fibril nucleus.
- Добавил в систему: Уверский Владимир Николаевич