TY - JOUR
T1 - Lipid Dynamics and Phase Transition within α-Synuclein Amyloid Fibrils
AU - Galvagnion, Céline
AU - Topgaard, Daniel
AU - Makasewicz, Katarzyna
AU - Buell, Alexander K
AU - Linse, Sara
AU - Sparr, Emma
AU - Dobson, Christopher M
N1 - This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
U2 - 10.1021/acs.jpclett.9b03005
DO - 10.1021/acs.jpclett.9b03005
M3 - Journal article
C2 - 31790267
SN - 1948-7185
VL - 10
SP - 7872
EP - 7877
JO - Journal of Physical Chemistry Letters
JF - Journal of Physical Chemistry Letters
ER -