Effects of Detergent on α-Synuclein Structure: A Native MS-Ion Mobility Study
| Autor: | Frank Sobott, Anne-Marie Lambeir, Stuart Maudsley, Renate van der Wekken-de Bruijne, Rani Moons, Filip Lemière |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular 0301 basic medicine Protein Conformation Micelle lcsh:Chemistry chemistry.chemical_compound 0302 clinical medicine Protein structure Nanotechnology lcsh:QH301-705.5 Spectroscopy mass spectrometry Neurodegeneration General Medicine Computer Science Applications Chemistry Monomer Membrane alpha-Synuclein Protein Binding Spectrometry Mass Electrospray Ionization ligand binding Electrospray ionization Detergents electrospray ionization Models Biological Article Catalysis Inorganic Chemistry 03 medical and health sciences ion mobility α-synuclein medicine Humans membrane interaction Molecule Physical and Theoretical Chemistry Biology Molecular Biology detergent micelles Organic Chemistry Biological membrane intrinsically disordered protein medicine.disease nervous system diseases 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 chemistry nervous system Biophysics Protein Multimerization 030217 neurology & neurosurgery |
| Zdroj: | International Journal of Molecular Sciences, Vol 21, Iss 7884, p 7884 (2020) International Journal of Molecular Sciences Volume 21 Issue 21 International journal of molecular science |
| ISSN: | 1661-6596 |
| Popis: | The intrinsically disordered protein &alpha synuclein plays a major role in Parkinson&rsquo 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. |
| Databáze: | OpenAIRE |
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