A structural and kinetic link between membrane association and amyloid fibril formation of α-Synuclein

Viennet, T.; Wördehoff, M. M.; Uluca, B.; Poojari, C.; Shaykhalishahi, H.; Willbold, D.; Strodel, B.; Heise, H.; Buell, A. K.; Hoyer, W.; Etzkorn, M.

doi:10.1101/173724

bioRxiv · 10.1101/173724

A structural and kinetic link between membrane association and amyloid fibril formation of α-Synuclein

Viennet, T.·Wördehoff, M. M.·Uluca, B.·Poojari, C.·Shaykhalishahi, H.·Willbold, D.·Strodel, B.·Heise, H.·Buell, A. K.·Hoyer, W.·Etzkorn, M.

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Abstract

The protein -Synuclein (S) is linked to Parkinsons disease through its abnormal aggregation, which is thought to involve an interplay between cytosolic and membrane-bound forms of S. Therefore, better insights into the molecular determinants of membrane association and their implications for protein aggregation may help deciphering the pathogenesis of Parkinsons disease. Following previous studies using micelles and vesicles, we present a comprehensive study of S interaction with phospholipid bilayer nanodiscs. Using a combination of NMR - spectroscopic and complementary biophysical as well as computational methods we structurally and kinetically characterize S interaction with defined stable planar membranes in a quantitative and site-resolved way. We probe the role of S acetylation as well as membrane charge, plasticity and available surface area in modulating S membrane binding modes and directly link these findings to their consequences for S amyloid fibril formation.

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Viennet, T., Wördehoff, M. M., Uluca, B., Poojari, C., Shaykhalishahi, H., Willbold, D., Strodel, B., Heise, H., Buell, A. K., Hoyer, W., Etzkorn, M.. 2017-08-08. A structural and kinetic link between membrane association and amyloid fibril formation of α-Synuclein. https://doi.org/10.1101/173724

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