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Untwisted α-Synuclein Filaments Formed in the Presence of Lipid Vesicles.

Publication ,  Journal Article
Dasari, AKR; Dillard, L; Yi, S; Viverette, E; Hojjatian, A; Sengupta, U; Kayed, R; Taylor, KA; Borgnia, MJ; Lim, KH
Published in: Biochemistry
September 6, 2022

Accumulation of filamentous aggregates of α-synuclein is a pathological hallmark of several neurodegenerative diseases, including Parkinson's disease (PD). The interaction between α-synuclein and phospholipids has been shown to play a critical role in the aggregation of α-synuclein. Most structural studies have, however, been focused on α-synuclein filaments formed in the absence of lipids. Here, we report the structural investigation of α-synuclein filaments assembled under the quiescent condition in the presence of anionic lipid vesicles using electron microscopy (EM), including cryogenic electron microscopy (cryo-EM). Our transmission electron microscopy (TEM) analyses reveal that α-synuclein forms curly protofilaments at an early stage of aggregation. The flexible protofilaments were then converted to long filaments after a longer incubation of 30 days. More detailed structural analyses using cryo-EM reveal that the long filaments adopt untwisted structures with different diameters, which have not been observed in previous α-synuclein fibrils formed in vitro. The untwisted filaments are rather similar to straight filaments with no observable twist that are extracted from patients with dementia with Lewy bodies. Our structural studies highlight the conformational diversity of α-synuclein filaments, requiring additional structural investigation of not only more ex vivo α-synuclein filaments but also in vitro α-synuclein filaments formed in the presence of diverse cofactors to better understand the molecular basis of diverse molecular conformations of α-synuclein filaments.

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Published In

Biochemistry

DOI

EISSN

1520-4995

Publication Date

September 6, 2022

Volume

61

Issue

17

Start / End Page

1766 / 1773

Location

United States

Related Subject Headings

  • alpha-Synuclein
  • Phospholipids
  • Parkinson Disease
  • Lewy Bodies
  • Humans
  • Cryoelectron Microscopy
  • Biochemistry & Molecular Biology
  • 3404 Medicinal and biomolecular chemistry
  • 3205 Medical biochemistry and metabolomics
  • 3101 Biochemistry and cell biology
 

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Dasari, A. K. R., Dillard, L., Yi, S., Viverette, E., Hojjatian, A., Sengupta, U., … Lim, K. H. (2022). Untwisted α-Synuclein Filaments Formed in the Presence of Lipid Vesicles. Biochemistry, 61(17), 1766–1773. https://doi.org/10.1021/acs.biochem.2c00283
Dasari, Anvesh K. R., Lucas Dillard, Sujung Yi, Elizabeth Viverette, Alimohammad Hojjatian, Urmi Sengupta, Rakez Kayed, Kenneth A. Taylor, Mario Juan Borgnia, and Kwang Hun Lim. “Untwisted α-Synuclein Filaments Formed in the Presence of Lipid Vesicles.Biochemistry 61, no. 17 (September 6, 2022): 1766–73. https://doi.org/10.1021/acs.biochem.2c00283.
Dasari AKR, Dillard L, Yi S, Viverette E, Hojjatian A, Sengupta U, et al. Untwisted α-Synuclein Filaments Formed in the Presence of Lipid Vesicles. Biochemistry. 2022 Sep 6;61(17):1766–73.
Dasari, Anvesh K. R., et al. “Untwisted α-Synuclein Filaments Formed in the Presence of Lipid Vesicles.Biochemistry, vol. 61, no. 17, Sept. 2022, pp. 1766–73. Pubmed, doi:10.1021/acs.biochem.2c00283.
Dasari AKR, Dillard L, Yi S, Viverette E, Hojjatian A, Sengupta U, Kayed R, Taylor KA, Borgnia MJ, Lim KH. Untwisted α-Synuclein Filaments Formed in the Presence of Lipid Vesicles. Biochemistry. 2022 Sep 6;61(17):1766–1773.
Journal cover image

Published In

Biochemistry

DOI

EISSN

1520-4995

Publication Date

September 6, 2022

Volume

61

Issue

17

Start / End Page

1766 / 1773

Location

United States

Related Subject Headings

  • alpha-Synuclein
  • Phospholipids
  • Parkinson Disease
  • Lewy Bodies
  • Humans
  • Cryoelectron Microscopy
  • Biochemistry & Molecular Biology
  • 3404 Medicinal and biomolecular chemistry
  • 3205 Medical biochemistry and metabolomics
  • 3101 Biochemistry and cell biology