Abstract
Previous studies indicate that binding of alpha-synuclein to membranes is critical for its physiological function and the development of Parkinson's disease (PD). Here, we have investigated the association of fluorescence-labeled alpha-synuclein variants with different types of giant unilamellar vesicles using confocal microscopy. We found that alpha-synuclein binds with high affinity to anionic phospholipids, when they are embedded in a liquid-disordered as opposed to a liquid-ordered environment. This indicates that not only electrostatic forces but also lipid packing and hydrophobic interactions are critical for the association of alpha-synuclein with membranes in vitro. When compared to wild-type alpha-synuclein, the disease-causing alpha-synuclein variant A30P bound less efficiently to anionic phospholipids, while the variant E46K showed enhanced binding. This suggests that the natural association of alpha-synuclein with membranes is altered in the inherited forms of Parkinson's disease.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Anions / metabolism*
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Binding Sites
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Cell Membrane / metabolism
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Fatty Acids / chemistry
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Fluorescent Dyes / metabolism
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Hydrophobic and Hydrophilic Interactions
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Lipids / chemistry
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Microscopy, Fluorescence
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Molecular Sequence Data
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Molecular Weight
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Mutation
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Parkinson Disease / genetics
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Phosphatidic Acids / chemistry
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Phosphatidylcholines / chemistry
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Phosphatidylcholines / metabolism
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Phosphatidylglycerols / chemistry
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Phosphatidylinositol 4,5-Diphosphate / chemistry
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Phosphatidylserines / chemistry
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Phospholipids / chemistry*
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Phospholipids / metabolism*
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Protein Binding
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Protein Conformation
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Rhodamines / metabolism
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Static Electricity
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Surface Properties
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Unilamellar Liposomes / chemistry
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Unilamellar Liposomes / metabolism
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alpha-Synuclein / chemistry
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alpha-Synuclein / genetics
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alpha-Synuclein / isolation & purification
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alpha-Synuclein / metabolism*
Substances
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Anions
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Fatty Acids
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Fluorescent Dyes
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Lipids
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Phosphatidic Acids
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Phosphatidylcholines
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Phosphatidylglycerols
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Phosphatidylinositol 4,5-Diphosphate
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Phosphatidylserines
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Phospholipids
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Rhodamines
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Unilamellar Liposomes
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alpha-Synuclein
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dioleoylphosphatidic acid
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tetramethylrhodamine
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1,2-dioleoyl-sn-glycero-3-phosphoglycerol
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1,2-dioleoylphosphatidylserine
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1-palmitoyl-2-(6-(N-(7-nitrobenz)-2-oxa-1,3-diazol-4-yl)aminocaproyl)phosphatidylcholine
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1,2-oleoylphosphatidylcholine