title: Alpha-synuclein binds to the inner membrane of mitochondria in an α-helical conformation.
abstract: The human alpha-Synuclein (αS) protein is of significant interest because of its association with Parkinson's disease and related neurodegenerative disorders. The intrinsically disordered protein (140 amino acids) is characterized by the absence of a well-defined structure in solution. It displays remarkable conformational flexibility upon macromolecular interactions, and can associate with mitochondrial membranes. Site-directed spin-labeling in combination with electron paramagnetic resonance spectroscopy enabled us to study the local binding properties of αS on artificial membranes (mimicking the inner and outer mitochondrial membranes), and to evaluate the importance of cardiolipin in this interaction. With pulsed, two-frequency, double-electron electron paramagnetic resonance (DEER) approaches, we examined, to the best of our knowledge for the first time, the conformation of αS bound to isolated mitochondria.
authors.affiliation: Department of Chemistry and Biology, Konstanz Research School Chemical Biology (KoRS-CB) and the Zukunftskolleg, University of Konstanz, 78457 Konstanz (Germany).
authors.forename: Marta
authors.initials: M
authors.lastname: Robotta
authors.forename: Hanne R
authors.initials: HR
authors.lastname: Gerding
authors.forename: Antonia
authors.initials: A
authors.lastname: Vogel
authors.forename: Karin
authors.initials: K
authors.lastname: Hauser
authors.forename: Stefan
authors.initials: S
authors.lastname: Schildknecht
authors.forename: Christiaan
authors.initials: C
authors.lastname: Karreman
authors.forename: Marcel
authors.initials: M
authors.lastname: Leist
authors.forename: Vinod
authors.initials: V
authors.lastname: Subramaniam
authors.forename: Malte
authors.initials: M
authors.lastname: Drescher
mesh_terms: D001665:Binding Sites; D057809:HEK293 Cells; D006801:Humans; D008928:Mitochondria / Q000737:chemistry* / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein
keywords: DEER; alpha-synuclein; helical structures; membranes; mitochondria; site-directed spin labeling