Probing conformational change of intrinsically disordered α-synuclein to helical structures by distinctive regional interactions with lipid membranes

Shin Jung C Lee, Jong Wha Lee, Tae Su Choi, Kyeong Sik Jin, Seonghwan Lee, Changill Ban, Hugh I. Kim

Research output: Contribution to journalArticle

21 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1909-1916
Number of pages8
JournalAnalytical chemistry
Issue number3
Publication statusPublished - 2014 Feb 4
Externally publishedYes


ASJC Scopus subject areas

  • Analytical Chemistry

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