Aggregation conditions strongly influence the molecular composition of alpha-synuclein oligomers

N. Zijlstra, C. Blum, V. Subramaniam

Research output: Contribution to journalMeeting AbstractOther research output

Abstract

Growing evidence suggests that alpha-synuclein oligomeric aggregates are key players in the onset and progression of Parkinson’s disease. However, very little is known about the molecular details of these aggregates.
For large protein aggregates, such as alpha-synuclein oligomers, it is very difficult to determine the number of monomers that form an oligomer using conventional techniques. We developed a method that uses sub-stoichiometric labeling in combination with single-molecule photobleaching to determine the number of monomers per oligomer [1]. By using the exact label density, we can link the number of fluorescent labels per oligomer to the total number of monomers. Using this combination of techniques, we are even able to distinguish multiple distinct species present in the same sample and determine their respective compositions.
For oligomers formed under high concentrations of alphasynuclein, we find a single, well-defined species while for oligomers formed under the addition of dopamine, we find two distinct species. Although there are significant differences in the molecular composition of the oligomers formed under specific preparation conditions, the oligomers still have a well-defined composition.
Original languageEnglish
Pages (from-to)S200-S200
JournalEuropean biophysics journal
Volume42
Issue numberSuppl. 1
DOIs
Publication statusPublished - 2013
Event9th European Biophysics Congress, EBSA 2013 - Lisbon, Portugal
Duration: 13 Jul 201317 Jul 2013
Conference number: 9

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alpha-Synuclein
Photobleaching
Parkinson Disease
Dopamine
Protein Aggregates

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title = "Aggregation conditions strongly influence the molecular composition of alpha-synuclein oligomers",
abstract = "Growing evidence suggests that alpha-synuclein oligomeric aggregates are key players in the onset and progression of Parkinson’s disease. However, very little is known about the molecular details of these aggregates.For large protein aggregates, such as alpha-synuclein oligomers, it is very difficult to determine the number of monomers that form an oligomer using conventional techniques. We developed a method that uses sub-stoichiometric labeling in combination with single-molecule photobleaching to determine the number of monomers per oligomer [1]. By using the exact label density, we can link the number of fluorescent labels per oligomer to the total number of monomers. Using this combination of techniques, we are even able to distinguish multiple distinct species present in the same sample and determine their respective compositions.For oligomers formed under high concentrations of alphasynuclein, we find a single, well-defined species while for oligomers formed under the addition of dopamine, we find two distinct species. Although there are significant differences in the molecular composition of the oligomers formed under specific preparation conditions, the oligomers still have a well-defined composition.",
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Aggregation conditions strongly influence the molecular composition of alpha-synuclein oligomers. / Zijlstra, N.; Blum, C.; Subramaniam, V.

In: European biophysics journal, Vol. 42, No. Suppl. 1, 2013, p. S200-S200.

Research output: Contribution to journalMeeting AbstractOther research output

TY - JOUR

T1 - Aggregation conditions strongly influence the molecular composition of alpha-synuclein oligomers

AU - Zijlstra, N.

AU - Blum, C.

AU - Subramaniam, V.

PY - 2013

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N2 - Growing evidence suggests that alpha-synuclein oligomeric aggregates are key players in the onset and progression of Parkinson’s disease. However, very little is known about the molecular details of these aggregates.For large protein aggregates, such as alpha-synuclein oligomers, it is very difficult to determine the number of monomers that form an oligomer using conventional techniques. We developed a method that uses sub-stoichiometric labeling in combination with single-molecule photobleaching to determine the number of monomers per oligomer [1]. By using the exact label density, we can link the number of fluorescent labels per oligomer to the total number of monomers. Using this combination of techniques, we are even able to distinguish multiple distinct species present in the same sample and determine their respective compositions.For oligomers formed under high concentrations of alphasynuclein, we find a single, well-defined species while for oligomers formed under the addition of dopamine, we find two distinct species. Although there are significant differences in the molecular composition of the oligomers formed under specific preparation conditions, the oligomers still have a well-defined composition.

AB - Growing evidence suggests that alpha-synuclein oligomeric aggregates are key players in the onset and progression of Parkinson’s disease. However, very little is known about the molecular details of these aggregates.For large protein aggregates, such as alpha-synuclein oligomers, it is very difficult to determine the number of monomers that form an oligomer using conventional techniques. We developed a method that uses sub-stoichiometric labeling in combination with single-molecule photobleaching to determine the number of monomers per oligomer [1]. By using the exact label density, we can link the number of fluorescent labels per oligomer to the total number of monomers. Using this combination of techniques, we are even able to distinguish multiple distinct species present in the same sample and determine their respective compositions.For oligomers formed under high concentrations of alphasynuclein, we find a single, well-defined species while for oligomers formed under the addition of dopamine, we find two distinct species. Although there are significant differences in the molecular composition of the oligomers formed under specific preparation conditions, the oligomers still have a well-defined composition.

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M3 - Meeting Abstract

VL - 42

SP - S200-S200

JO - European biophysics journal

JF - European biophysics journal

SN - 0175-7571

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ER -