Moons, R, van der Wekken-de Bruijne, R, Maudsley, S et al. (3 more authors) (2020) Effects of Detergent on α-Synuclein Structure: A Native MS-Ion Mobility Study. International Journal of Molecular Sciences, 21 (21). 7884. pp. 1-23. ISSN 1661-6596
Abstract
The intrinsically disordered protein α-synuclein plays a major role in Parkinson’s disease. The protein can oligomerize resulting in the formation of various aggregated species in neuronal cells, leading to neurodegeneration. The interaction of α-synuclein with biological cell membranes plays an important role for specific functions of α-synuclein monomers, e.g., in neurotransmitter release. Using different types of detergents to mimic lipid molecules present in biological membranes, including the presence of Ca2+ ions as an important structural factor, we aimed to gain an understanding of how α-synuclein interacts with membrane models and how this affects the protein conformation and potential oligomerization. We investigated detergent binding stoichiometry, affinity and conformational changes of α-synuclein taking detergent concentration, different detergent structures and charges into account. With native nano-electrospray ionization ion mobility-mass spectrometry, we were able to detect unique conformational patterns resulting from binding of specific detergents to α-synuclein. Our data demonstrate that α-synuclein monomers can interact with detergent molecules irrespective of their charge, that protein-micelle interactions occur and that micelle properties are an important factor.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | ion mobility; mass spectrometry; α-synuclein; intrinsically disordered protein; detergent micelles; membrane interaction; protein conformation; ligand binding; electrospray ionization |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 16 Nov 2020 15:10 |
Last Modified: | 16 Nov 2020 15:10 |
Status: | Published |
Publisher: | MDPI |
Identification Number: | 10.3390/ijms21217884 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:168018 |