α-Synuclein Interaction with Lipid Bilayer Discs

Published

August 23, 2022

Author(s)

Marija Dubackic, Yun Liu, Elizabeth Kelley, Crispin Hetherington, Michael Haertlein, Juliette Devos, Sara Linse, Emma Sparr, Ulf Olsson

Abstract

α-Synuclein (aSyn) is a 140 residue long protein that is present in presynaptic termini of nerve cells. The protein is also pathologically associated with Parkinson's disease, where it has been found to self-assemble into long amyloid fibrils forming intracellular inclusions that are also rich in lipids. Furthermore, its synaptic function involves interaction with lipid membranes and hence it is of interest to understand aSyn-lipid membrane interactions in detail. In this paper we report on the interaction of aSyn with a model membrane in the form of lipid disc micelles. Using a combination of cryo transmission electron microscopy and small angle neutron scattering, we show that approximately circular disc micelles undergo a significant shape transition after the adsorption of aSyn molecules. As aSyn then further self-assembles into fibrils, aSyn molecules desorb from the micelles, possibly by being recruited to fibrils, allowing the micelles to retain their original circular disc shape. Interestingly, the desorption from a micelle has an all-or-none character, resulting in a binary coexistence of circular disc micelles, with no adsorbed aSyn molecules, and micelles having a maximum adsorbed amount. The observed binary coexistence is consistent with the recent findings that aSyn adsorption to anionic lipid bilayers is a cooperative association.

Citation

Langmuir

Volume

38

Issue

33

Pub Type

Journals

Download Paper

DOI Link

Keywords

alpha-synuclein, lipid disc micelles, bicelles, small angle neutron scattering, fibrils, cooperative binding

Citation

Dubackic, M. , Liu, Y. , Kelley, E. , Hetherington, C. , Haertlein, M. , Devos, J. , Linse, S. , Sparr, E. and Olsson, U. (2022), α-Synuclein Interaction with Lipid Bilayer Discs, Langmuir, [online], https://dx.doi.org/10.1021/acs.langmuir.2c01368 (Accessed December 3, 2024)