PT  - JOURNAL ARTICLE
AU  - Viennet, Thibault
AU  - Wördehoff, Michael M.
AU  - Uluca, Boran
AU  - Poojari, Chetan
AU  - Shaykhalishahi, Hamed
AU  - Willbold, Dieter
AU  - Strodel, Birgit
AU  - Heise, Henrike
AU  - Buell, Alexander K.
AU  - Hoyer, Wolfgang
AU  - Etzkorn, Manuel
TI  - A structural and kinetic link between membrane association and amyloid fibril formation of α-Synuclein
AID  - 10.1101/173724
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 173724
4099  - http://biorxiv.org/content/early/2017/08/08/173724.short
4100  - http://biorxiv.org/content/early/2017/08/08/173724.full
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.