RT Journal Article
SR Electronic
T1 A structural and kinetic link between membrane association and amyloid fibril formation of α-Synuclein
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 173724
DO 10.1101/173724
A1 Viennet, Thibault
A1 Wördehoff, Michael M.
A1 Uluca, Boran
A1 Poojari, Chetan
A1 Shaykhalishahi, Hamed
A1 Willbold, Dieter
A1 Strodel, Birgit
A1 Heise, Henrike
A1 Buell, Alexander K.
A1 Hoyer, Wolfgang
A1 Etzkorn, Manuel
YR 2017
UL http://biorxiv.org/content/early/2017/08/08/173724.abstract
AB The protein α-Synuclein (αS) is linked to Parkinson’s disease through its abnormal aggregation, which is thought to involve an interplay between cytosolic and membrane-bound forms of αS. Therefore, better insights into the molecular determinants of membrane association and their implications for protein aggregation may help deciphering the pathogenesis of Parkinson’s disease. 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 and complementary biophysical as well as computational methods we structurally and kinetically characterize αS interaction with defined stable planar membranes in a quantitative and site-resolved way. We probe the role of αS acetylation as well as membrane charge, plasticity and available surface area in modulating αS membrane binding modes and directly link these findings to their consequences for αS amyloid fibril formation.