DOI: 10.1016/j.febslet.2004.09.038. Mutation E46K increases phospholipid binding and assembly into filaments of human α‐synuclein

Mutation E46K increases phospholipid binding and assembly into filaments of human α‐synuclein

10.1016/j.febslet.2004.09.038

Crossref journal-article

Wiley

FEBS Letters (311)

Abstract

Missense mutations (A30P and A53T) in α‐synuclein and the overproduction of the wild‐type protein cause familial forms of Parkinson's disease and dementia with Lewy bodies. α‐Synuclein is the major component of the filamentous Lewy bodies and Lewy neurites that define these diseases at a neuropathological level. Recently, a third missense mutation (E46K) in α‐synuclein was described in an inherited form of dementia with Lewy bodies. Here, we have investigated the functional effects of this novel mutation on phospholipid binding and filament assembly of α‐synuclein. When compared to the wild‐type protein, the E46K mutation caused a significantly increased ability of α‐synuclein to bind to negatively charged liposomes, unlike the previously described mutations. The E46K mutation increased the rate of filament assembly to the same extent as the A53T mutation. Filaments formed from E46K α‐synuclein often had a twisted morphology with a cross‐over spacing of 43 nm. The observed effects on lipid binding and filament assembly may explain the pathogenic nature of the E46K mutation in α‐synuclein.

Bibliography

Choi, W., Zibaee, S., Jakes, R., Serpell, L. C., Davletov, B., Anthony Crowther, R., & Goedert, M. (2004). Mutation E46K increases phospholipid binding and assembly into filaments of human Î±âsynuclein. FEBS Letters, 576(3), 363â368. Portico.

Authors 7

Woong Choi (first)
Shahin Zibaee (additional)
Ross Jakes (additional)
Louise C. Serpell (additional)
Bazbek Davletov (additional)
R. Anthony Crowther (additional)
Michel Goedert (additional)

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Dates

Type	When
Created	20 years, 10 months ago (Sept. 28, 2004, 11:28 a.m.)
Deposited	1 year, 11 months ago (Sept. 17, 2023, 10:39 p.m.)
Indexed	3 weeks, 4 days ago (Aug. 2, 2025, 12:30 a.m.)
Issued	20 years, 11 months ago (Sept. 25, 2004)
Published	20 years, 11 months ago (Sept. 25, 2004)
Published Online	20 years, 11 months ago (Sept. 25, 2004)
Published Print	20 years, 10 months ago (Oct. 22, 2004)

Funders 0

None

BibTeX

@article{Choi_2004, title={Mutation E46K increases phospholipid binding and assembly into filaments of human α‐synuclein}, volume={576}, ISSN={1873-3468}, url={http://dx.doi.org/10.1016/j.febslet.2004.09.038}, DOI={10.1016/j.febslet.2004.09.038}, number={3}, journal={FEBS Letters}, publisher={Wiley}, author={Choi, Woong and Zibaee, Shahin and Jakes, Ross and Serpell, Louise C. and Davletov, Bazbek and Anthony Crowther, R. and Goedert, Michel}, year={2004}, month=sep, pages={363–368} }

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