TY - JOUR T1 - A structural and kinetic link between membrane association and amyloid fibril formation of α-Synuclein JF - bioRxiv DO - 10.1101/173724 SP - 173724 AU - Thibault Viennet AU - Michael M. Wördehoff AU - Boran Uluca AU - Chetan Poojari AU - Hamed Shaykhalishahi AU - Dieter Willbold AU - Birgit Strodel AU - Henrike Heise AU - Alexander K. Buell AU - Wolfgang Hoyer AU - Manuel Etzkorn Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/08/08/173724.abstract N2 - 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. ER -