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Cited by 604

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α-Synuclein Membrane Interactions and Lipid Specificity

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Jo, Euijung, McLaurin, JoAnne, Yip, Christopher M., St. George-Hyslop, Peter, Fraser, Paul E.·2000·Journal of Biological Chemistry
DOI 10.1074/jbc.m004345200
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Abstract

With the discovery of missense mutations (A53T and A30P) in alpha-synuclein (alpha-Syn) in several families with early onset familial Parkinson's disease, alpha-Syn aggregation and fibril formation have been thought to play a role in the pathogenesis of alpha-synucleinopathies, such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. As previous reports have suggested that alpha-Syn plays a role in lipid transport and synaptic membrane biogenesis, we investigated whether alpha-Syn binds to a specific lipid ligand using thin layer chromatography overlay and examined the changes in its secondary structure using circular dichroism spectroscopy. alpha-Syn was found to bind to acidic phospholipid vesicles and this binding was significantly augmented by the presence of phosphatidylethanolamine, a neutral phospholipid. We further examined the interaction of alpha-Syn with lipids by in situ atomic force microscopy. The association of soluble wild-type alpha-Syn with planar lipid bilayers resulted in extensive bilayer disruption and the formation of amorphous aggregates and small fibrils. The A53T mutant alpha-Syn disrupted the lipid bilayers in a similar fashion but at a slower rate. These results suggest that alpha-Syn membrane interactions are physiologically important and the lipid composition of the cellular membranes may affect these interactions in vivo.

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Metadata

Authors
Jo, E., McLaurin, J., Yip, C. M., St. George-Hyslop, P., & Fraser, P. E.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2000-11
Volume
275
Issue
44
Pages
34328-34334
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.m004345200
OpenAlex
W1517181973
Cited by
604
References
8
FWCI
11.10
Type
journal article
Language
en
Open access
hybrid
Licence

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CoChat. (2026). Citation check: α-Synuclein Membrane Interactions and Lipid Specificity. https://app.cochat.ai/papers/10.1074/jbc.m004345200
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Jo, E., McLaurin, J., Yip, C. M., St. George-Hyslop, P., & Fraser, P. E. (2000). α-Synuclein Membrane Interactions and Lipid Specificity. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m004345200

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