Effects of Detergent on α-Synuclein Structure. A Native MS-Ion Mobility Study

International Journal of Molecular Sciences

Filip Lemière¹  Renatevan der Wekken-de Bruijne¹  Rani Moons¹  Frank Sobott¹  Anne-Marie Lambeir²  Stuart Maudsley³ 

[1] Biomolecular and Analytical Mass Spectrometry Group, University of Antwerp, 2020 Antwerp, Belgium;Laboratory of Medical Biochemistry, University of Antwerp, 2610 Antwerp, Belgium;Receptor Biology Lab, University of Antwerp, 2610 Antwerp, Belgium;

关键词: ion mobility;    mass spectrometry;    α-synuclein;    intrinsically disordered protein;    detergent micelles;    membrane interaction;   

DOI  :  10.3390/ijms21217884

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown