title: Parkinson's Protein α-Synuclein Binds Efficiently and with a Novel Conformation to Two Natural Membrane Mimics.
abstract: Binding of human α-Synuclein, a protein associated with Parkinson's disease, to natural membranes is thought to be crucial in relation to its pathological and physiological function. Here the binding of αS to small unilamellar vesicles mimicking the inner mitochondrial and the neuronal plasma membrane is studied in situ by continuous wave and pulsed electron paramagnetic resonance. Local binding information of αS spin labeled by MTSL at positions 56 and 69 respectively shows that also helix 2 (residues 50-100) binds firmly to both membranes. By double electron-electron resonance (DEER) on the mutant spin labeled at positions 27 and 56 (αS 27/56) a new conformation on the membrane is found with a distance of 3.6 nm/ 3.7 nm between residues 27 and 56. In view of the low negative charge density of these membranes, the strong interaction is surprising, emphasizing that function and pathology of αS could involve synaptic vesicles and mitochondria.
authors.affiliation: Department of Physics, Huygens-Kammerlingh-Onnes Laboratory, Leiden University, Leiden, The Netherlands.
authors.forename: Pravin
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Nanobiophysics, MESA+ Institute for Nanotechnology, University of Twente, Enschede, The Netherlands.
authors.forename: Ine M J
authors.initials: IM
authors.lastname: Segers-Nolten
authors.affiliation: Nanobiophysics, MESA+ Institute for Nanotechnology, University of Twente, Enschede, The Netherlands.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Schilderink
authors.affiliation: Nanobiophysics, MESA+ Institute for Nanotechnology, University of Twente, Enschede, The Netherlands.|FOM Institute AMOLF, Amsterdam, The Netherlands.
authors.forename: Vinod
authors.initials: V
authors.lastname: Subramaniam
authors.affiliation: Department of Physics, Huygens-Kammerlingh-Onnes Laboratory, Leiden University, Leiden, The Netherlands.
authors.forename: Martina
authors.initials: M
authors.lastname: Huber
mesh_terms: D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000737:chemistry* / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000737:chemistry / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D011487:Protein Conformation; D013572:Synaptic Vesicles / Q000737:chemistry / Q000378:metabolism; D053835:Unilamellar Liposomes / Q000737:chemistry* / Q000378:metabolism; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism
chemical_list: D053835:Unilamellar Liposomes; D051844:alpha-Synuclein