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Lipid Dynamics and Phase Transition within α-Synuclein Amyloid Fibrils

Galvagnion, Céline ; Topgaard, Daniel LU ; Makasewicz, Katarzyna LU ; Buell, Alexander K. ; Linse, Sara LU ; Sparr, Emma LU and Dobson, Christopher M. (2019) In Journal of Physical Chemistry Letters 10(24). p.7872-7877
Abstract

The deposition of coassemblies made of the small presynaptic protein, α-synuclein, and lipids in the brains of patients is the hallmark of Parkinson's disease. In this study, we used natural abundance 13C and 31P magic-angle spinning nuclear magnetic resonance spectroscopy together with cryo-electron microscopy and differential scanning calorimetry to characterize the fibrils formed by α-synuclein in the presence of vesicles made of 1,2-dimyristoyl-sn-glycero-3-phospho-L-serine or 1,2-dilauroyl-sn-glycero-3-phospho-L-serine. Our results show that these lipids coassemble with α-synuclein molecules to give thin and curly amyloid fibrils. The coassembly leads to slower and more isotropic reorientation of lipid... (More)

The deposition of coassemblies made of the small presynaptic protein, α-synuclein, and lipids in the brains of patients is the hallmark of Parkinson's disease. In this study, we used natural abundance 13C and 31P magic-angle spinning nuclear magnetic resonance spectroscopy together with cryo-electron microscopy and differential scanning calorimetry to characterize the fibrils formed by α-synuclein in the presence of vesicles made of 1,2-dimyristoyl-sn-glycero-3-phospho-L-serine or 1,2-dilauroyl-sn-glycero-3-phospho-L-serine. Our results show that these lipids coassemble with α-synuclein molecules to give thin and curly amyloid fibrils. The coassembly leads to slower and more isotropic reorientation of lipid molecular segments and a decrease in both the temperature and enthalpy of the lipid chain-melting compared with those in the protein-free lipid lamellar phase. These findings provide new insights into the properties of lipids within protein-lipid assemblies that can be associated with Parkinson's disease.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Physical Chemistry Letters
volume
10
issue
24
pages
6 pages
publisher
The American Chemical Society (ACS)
external identifiers
  • scopus:85076779245
  • pmid:31790267
ISSN
1948-7185
DOI
10.1021/acs.jpclett.9b03005
language
English
LU publication?
yes
id
75636894-eb0e-4cbe-acc4-3c31a5706126
date added to LUP
2020-01-10 10:44:35
date last changed
2021-04-13 05:16:39
@article{75636894-eb0e-4cbe-acc4-3c31a5706126,
  abstract     = {<p>The deposition of coassemblies made of the small presynaptic protein, α-synuclein, and lipids in the brains of patients is the hallmark of Parkinson's disease. In this study, we used natural abundance <sup>13</sup>C and <sup>31</sup>P magic-angle spinning nuclear magnetic resonance spectroscopy together with cryo-electron microscopy and differential scanning calorimetry to characterize the fibrils formed by α-synuclein in the presence of vesicles made of 1,2-dimyristoyl-sn-glycero-3-phospho-L-serine or 1,2-dilauroyl-sn-glycero-3-phospho-L-serine. Our results show that these lipids coassemble with α-synuclein molecules to give thin and curly amyloid fibrils. The coassembly leads to slower and more isotropic reorientation of lipid molecular segments and a decrease in both the temperature and enthalpy of the lipid chain-melting compared with those in the protein-free lipid lamellar phase. These findings provide new insights into the properties of lipids within protein-lipid assemblies that can be associated with Parkinson's disease.</p>},
  author       = {Galvagnion, Céline and Topgaard, Daniel and Makasewicz, Katarzyna and Buell, Alexander K. and Linse, Sara and Sparr, Emma and Dobson, Christopher M.},
  issn         = {1948-7185},
  language     = {eng},
  month        = {12},
  number       = {24},
  pages        = {7872--7877},
  publisher    = {The American Chemical Society (ACS)},
  series       = {Journal of Physical Chemistry Letters},
  title        = {Lipid Dynamics and Phase Transition within α-Synuclein Amyloid Fibrils},
  url          = {http://dx.doi.org/10.1021/acs.jpclett.9b03005},
  doi          = {10.1021/acs.jpclett.9b03005},
  volume       = {10},
  year         = {2019},
}