title: Probing conformational change of intrinsically disordered α-synuclein to helical structures by distinctive regional interactions with lipid membranes.
abstract: α-Synuclein (α-Syn) is an intrinsically disordered protein, whose fibrillar aggregates are associated with the pathogenesis of Parkinson's disease. α-Syn associates with lipid membranes and forms helical structures upon membrane binding. In this study, we explored the helix formation of α-Syn in solution containing trifluoroethanol using small-angle X-ray scattering and electrospray ionization ion mobility mass spectrometry. We then investigated the structural transitions of α-Syn to helical structures via association with large unilamellar vesicles as model lipid membrane systems. Hydrogen-deuterium exchange combined with electrospray ionization mass spectrometry was further utilized to understand the details of the regional interaction mechanisms of α-Syn with lipid vesicles based on the polarity of the lipid head groups. The characteristics of the helical structures were observed with α-Syn by adsorption onto the anionic phospholipid vesicles via electrostatic interactions between the N-terminal region of the protein and the anionic head groups of the lipids. α-Syn also associates with zwitterionic lipid vesicles and forms helical structures via hydrophobic interactions. These experimental observations provide an improved understanding of the distinct structural change mechanisms of α-Syn that originate from different regional interactions of the protein with lipid membranes and subsequently provide implications regarding diverse protein-membrane interactions related to their fibrillation kinetics.
authors.affiliation: Department of Chemistry, ‡Pohang Accelerator Laboratory, §Division of Advanced Materials Science, Pohang University of Science and Technology (POSTECH) , Pohang, North Gyeongsang 790-784, South Korea.
authors.forename: Shin Jung C
authors.initials: SJ
authors.lastname: Lee
authors.forename: Jong Wha
authors.initials: JW
authors.lastname: Lee
authors.forename: Tae Su
authors.initials: TS
authors.lastname: Choi
authors.forename: Kyeong Sik
authors.initials: KS
authors.lastname: Jin
authors.forename: Seonghwan
authors.initials: S
authors.lastname: Lee
authors.forename: Changill
authors.initials: C
authors.lastname: Ban
authors.forename: Hugh I
authors.initials: HI
authors.lastname: Kim
mesh_terms: D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D053835:Unilamellar Liposomes / Q000737:chemistry / Q000378:metabolism; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D008051:Lipid Bilayers; D010743:Phospholipids; D053835:Unilamellar Liposomes; D051844:alpha-Synuclein