Alfa-Synüklein membran birliği ve amiloid fibril oluşumu arasında yapısal ve kinetik bir bağlantı

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ABSTRACT 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.

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