Effects of detergent on α-synuclein structure

Subtitle:a native MS-ion mobility study

The intrinsically disordered protein alpha-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 alpha-synuclein with biological cell membranes plays an important role for specific functions of alpha-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 alpha-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 alpha-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 alpha-synuclein. Our data demonstrate that alpha-synuclein monomers can interact with detergent molecules irrespective of their charge, that protein-micelle interactions occur and that micelle properties are an important factor.

Publication year:2020

Keywords:A1 Journal article

BOF-keylabel:yes

BOF-publication weight:1

CSS-citation score:1

Authors:International

Authors from:Higher Education

Accessibility:Open