This title appears in the Scientific Report :
2018
Please use the identifier:
http://hdl.handle.net/2128/19846 in citations.
Please use the identifier: http://dx.doi.org/10.1038/s42003-018-0049-z in citations.
Structural insights from lipid-bilayer nanodiscs link α-Synuclein membrane-binding modes to amyloid fibril formation
Structural insights from lipid-bilayer nanodiscs link α-Synuclein membrane-binding modes to amyloid fibril formation
The protein α-Synuclein (αS) is linked to Parkinson’s disease through its abnormal aggregation, which is thought to involve cytosolic and membrane-bound forms of αS. Following previous studies using micelles and vesicles, we present a comprehensive study of αS interaction with phospholipid bilayer n...
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Personal Name(s): | Viennet, Thibault |
---|---|
Wördehoff, Michael M. / Uluca, Boran / Poojari, Chetan / Shaykhalishahi, Hamed / Willbold, Dieter / Strodel, Birgit / Heise, Henrike / Buell, Alexander K. / Hoyer, Wolfgang / Etzkorn, Manuel (Corresponding author) | |
Contributing Institute: |
Strukturbiochemie; ICS-6 |
Published in: | Communications biology, 1 (2018) 1, S. 44 |
Imprint: |
London
Springer Nature
2018
|
DOI: |
10.1038/s42003-018-0049-z |
PubMed ID: |
30271927 |
Document Type: |
Journal Article |
Research Program: |
Functional Macromolecules and Complexes |
Link: |
OpenAccess OpenAccess |
Publikationsportal JuSER |
Please use the identifier: http://dx.doi.org/10.1038/s42003-018-0049-z in citations.
The protein α-Synuclein (αS) is linked to Parkinson’s disease through its abnormal aggregation, which is thought to involve cytosolic and membrane-bound forms of αS. Following previous studies using micelles and vesicles, we present a comprehensive study of αS interaction with phospholipid bilayer nanodiscs. Using a combination of NMR-spectroscopic, biophysical, and computational methods, we structurally and kinetically characterize αS interaction with different membrane discs in a quantitative and site-resolved way. We obtain global and residue-specific αS membrane affinities, and determine modulations of αS membrane binding due to αS acetylation, membrane plasticity, lipid charge density, and accessible membrane surface area, as well as the consequences of the different binding modes for αS amyloid fibril formation. Our results establish a structural and kinetic link between the observed dissimilar binding modes and either aggregation-inhibiting properties, largely unperturbed aggregation, or accelerated aggregation due to membrane-assisted fibril nucleation. |