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Chemical properties of lipids strongly affect the kinetics of the membrane-induced aggregation of α-synuclein

Galvagnion, Céline; Brown, James W P; Ouberai, Myriam M.; Flagmeier, Patrick; Vendruscolo, Michele; Buell, Alexander K.; Sparr, Emma LU and Dobson, Christopher M. (2016) In Proceedings of the National Academy of Sciences of the United States of America 113(26). p.7065-7070
Abstract

Intracellular α-synuclein deposits, known as Lewy bodies, have been linked to a range of neurodegenerative disorders, including Parkinson's disease. α-Synuclein binds to synthetic and biological lipids, and this interaction has been shown to play a crucial role for both α-synuclein's native function, including synaptic plasticity, and the initiation of its aggregation. Here, we describe the interplay between the lipid properties and the lipid binding and aggregation propensity of α-synuclein. In particular, we have observed that the binding of α-synuclein to model membranes is much stronger when the latter is in the fluid rather than the gel phase, and that this binding induces a segregation of the lipids into protein-poor and... (More)

Intracellular α-synuclein deposits, known as Lewy bodies, have been linked to a range of neurodegenerative disorders, including Parkinson's disease. α-Synuclein binds to synthetic and biological lipids, and this interaction has been shown to play a crucial role for both α-synuclein's native function, including synaptic plasticity, and the initiation of its aggregation. Here, we describe the interplay between the lipid properties and the lipid binding and aggregation propensity of α-synuclein. In particular, we have observed that the binding of α-synuclein to model membranes is much stronger when the latter is in the fluid rather than the gel phase, and that this binding induces a segregation of the lipids into protein-poor and protein-rich populations. In addition, α-synuclein was found to aggregate at detectable rates only when interacting with membranes composed of the most soluble lipids investigated here. Overall, our results show that the chemical properties of lipids determine whether or not the lipids can trigger the aggregation of α-synuclein, thus affecting the balance between functional and aberrant behavior of the protein.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Lipid-induced aggregation, Parkinson's disease, Phase diagram, α-synuclein
in
Proceedings of the National Academy of Sciences of the United States of America
volume
113
issue
26
pages
6 pages
publisher
National Acad Sciences
external identifiers
  • scopus:84976602130
  • wos:000379033400042
ISSN
0027-8424
DOI
10.1073/pnas.1601899113
language
English
LU publication?
yes
id
7c73e1f1-f7bd-4244-9fb0-82c34f32feeb
date added to LUP
2017-01-19 13:39:30
date last changed
2017-09-18 11:32:41
@article{7c73e1f1-f7bd-4244-9fb0-82c34f32feeb,
  abstract     = {<p>Intracellular α-synuclein deposits, known as Lewy bodies, have been linked to a range of neurodegenerative disorders, including Parkinson's disease. α-Synuclein binds to synthetic and biological lipids, and this interaction has been shown to play a crucial role for both α-synuclein's native function, including synaptic plasticity, and the initiation of its aggregation. Here, we describe the interplay between the lipid properties and the lipid binding and aggregation propensity of α-synuclein. In particular, we have observed that the binding of α-synuclein to model membranes is much stronger when the latter is in the fluid rather than the gel phase, and that this binding induces a segregation of the lipids into protein-poor and protein-rich populations. In addition, α-synuclein was found to aggregate at detectable rates only when interacting with membranes composed of the most soluble lipids investigated here. Overall, our results show that the chemical properties of lipids determine whether or not the lipids can trigger the aggregation of α-synuclein, thus affecting the balance between functional and aberrant behavior of the protein.</p>},
  author       = {Galvagnion, Céline and Brown, James W P and Ouberai, Myriam M. and Flagmeier, Patrick and Vendruscolo, Michele and Buell, Alexander K. and Sparr, Emma and Dobson, Christopher M.},
  issn         = {0027-8424},
  keyword      = {Lipid-induced aggregation,Parkinson's disease,Phase diagram,α-synuclein},
  language     = {eng},
  month        = {06},
  number       = {26},
  pages        = {7065--7070},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences of the United States of America},
  title        = {Chemical properties of lipids strongly affect the kinetics of the membrane-induced aggregation of α-synuclein},
  url          = {http://dx.doi.org/10.1073/pnas.1601899113},
  volume       = {113},
  year         = {2016},
}