2. Academic Validation
  3. Lipid Dynamics and Phase Transition within α-Synuclein Amyloid Fibrils

Lipid Dynamics and Phase Transition within α-Synuclein Amyloid Fibrils

  • J Phys Chem Lett. 2019 Dec 19;10(24):7872-7877. doi: 10.1021/acs.jpclett.9b03005.
Céline Galvagnion 1 2,  Daniel Topgaard 3,  Katarzyna Makasewicz 3,  Alexander K Buell 4,  Sara Linse 5,  Emma Sparr 3,  Christopher M Dobson 1
Affiliations

Affiliations

  • 1 Centre for Misfolding Diseases, Department of Chemistry , University of Cambridge , Lensfield Road , Cambridge CB2 1EW , United Kingdom.
  • 2 German Center for Neurodegenerative Diseases , Sigmund-Freud-Str. 27 , 53127 Bonn , Germany.
  • 3 Division of Physical Chemistry, Center for Chemistry and Chemical Engineering , Lund University , P.O. Box 124, SE-22100 Lund , Sweden.
  • 4 Department of Biotechnology and Biomedicine, DTU Bioengineering , Technical University of Denmark , Soltofts Plads 227 , DK-2800 Kgs. Lyngby , Denmark.
  • 5 Department of Biochemistry and Structural Biology , Lund University , SE-22100 Lund , Sweden.
PMID: 31790267 DOI: 10.1021/acs.jpclett.9b03005
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 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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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-W440985
    Liposome