title: 19F NMR studies of α-synuclein-membrane interactions.
abstract: α-Synuclein function is thought to be related to its membrane binding ability. Solution NMR studies have identified several α-synuclein-membrane interaction modes in small unilamellar vesicles (SUVs), but how membrane properties affect binding remains unclear. Here, we use (19)F NMR to study α-synuclein-membrane interactions by using 3-fluoro-L-tyrosine (3FY) and trifluoromethyl-L-phenylalanine (tfmF) labeled proteins. Our results indicate that the affinity is affected by both the head group and the acyl chain of the SUV. Negatively charged head groups have higher affinity, but different head groups with the same charge also affect binding. We show that the saturation of the acyl chain has a dramatic effect on the α-synuclein-membrane interactions by studying lipids with the same head group but different chains. Taken together, the data show that α-synuclein's N-terminal region is the most important determinate of SUV binding, but its C-terminal region also modulates the interactions. Our data support the existence of multiple tight phospholipid-binding modes, a result incompatible with the model that α-synuclein lies solely on the membrane surface.
authors.affiliation: Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Gui-Fang
authors.initials: GF
authors.lastname: Wang
authors.forename: Conggang
authors.initials: C
authors.lastname: Li
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Pielak
mesh_terms: D000595:Amino Acid Sequence; D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008823:Micelles; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011485:Protein Binding; D053835:Unilamellar Liposomes / Q000737:chemistry / Q000378:metabolism*; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D005462:Fluorine Radioisotopes; D008055:Lipids; D008823:Micelles; D053835:Unilamellar Liposomes; D051844:alpha-Synuclein