DOI: 10.1073/pnas.97.9.4897. Fiber diffraction of synthetic α-synuclein filaments shows amyloid-like cross-β conformation

Fiber diffraction of synthetic α-synuclein filaments shows amyloid-like cross-β conformation

10.1073/pnas.97.9.4897

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Filamentous inclusions made of α-synuclein constitute the defining neuropathological characteristic of Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Rare familial cases of Parkinson's disease are associated with mutations A53T and A30P in α-synuclein. We report here the assembly properties and secondary structure characteristics of recombinant α-synuclein. Carboxy-terminally truncated human α-synuclein (1–87) and (1–120) showed the fastest rates of assembly, followed by human A53T α-synuclein, and rat and zebra finch α-synuclein. Wild-type human α-synuclein and the A30P mutant showed slower rates of assembly. Upon shaking, filaments formed within 48 h at 37°C. The related proteins β- and γ-synuclein only assembled after several weeks of incubation. Synthetic human α-synuclein filaments were decorated by an antibody directed against the carboxy-terminal 10 amino acids of α-synuclein, as were filaments extracted from dementia with Lewy bodies and multiple system atrophy brains. Circular dichroism spectroscopy indicated that α-synuclein undergoes a conformational change from random coil to β-sheet structure during assembly. X-ray diffraction and electron diffraction of the α-synuclein assemblies showed a cross-β conformation characteristic of amyloid.

Bibliography

Serpell, L. C., Berriman, J., Jakes, R., Goedert, M., & Crowther, R. A. (2000). Fiber diffraction of synthetic Î±-synuclein filaments shows amyloid-like cross-Î² conformation. Proceedings of the National Academy of Sciences, 97(9), 4897â4902.

Authors 5

Louise C. Serpell (first)
John Berriman (additional)
Ross Jakes (additional)
Michel Goedert (additional)
R. Anthony Crowther (additional)

References 55 Referenced 654

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Dates

Type	When
Created	23 years ago (July 26, 2002, 10:38 a.m.)
Deposited	1 year, 7 months ago (Jan. 3, 2024, 11:56 p.m.)
Indexed	4 weeks, 1 day ago (July 25, 2025, 6:33 a.m.)
Issued	25 years, 3 months ago (April 25, 2000)
Published	25 years, 3 months ago (April 25, 2000)
Published Online	25 years, 3 months ago (April 25, 2000)
Published Print	25 years, 3 months ago (April 25, 2000)

Funders 0

None

BibTeX

@article{Serpell_2000, title={Fiber diffraction of synthetic α-synuclein filaments shows amyloid-like cross-β conformation}, volume={97}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.97.9.4897}, DOI={10.1073/pnas.97.9.4897}, number={9}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Serpell, Louise C. and Berriman, John and Jakes, Ross and Goedert, Michel and Crowther, R. Anthony}, year={2000}, month=apr, pages={4897–4902} }

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      "value": "2000-04-25",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}