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)

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.

Original languageEnglish
Pages (from-to)1909-1916
Number of pages8
JournalAnalytical chemistry
Volume86
Issue number3
DOIs
Publication statusPublished - 2014 Feb 4
Externally publishedYes

Fingerprint

Synucleins
Membrane Lipids
Lipids
Electrospray ionization
Mass spectrometry
Intrinsically Disordered Proteins
Trifluoroethanol
Unilamellar Liposomes
Membrane structures
Deuterium
Coulomb interactions
X ray scattering
Hydrogen
Phospholipids
Membrane Proteins
Proteins
Association reactions
Ions
Adsorption
Kinetics

ASJC Scopus subject areas

  • Analytical Chemistry

Cite this

Probing conformational change of intrinsically disordered α-synuclein to helical structures by distinctive regional interactions with lipid membranes. / Lee, Shin Jung C; Lee, Jong Wha; Choi, Tae Su; Jin, Kyeong Sik; Lee, Seonghwan; Ban, Changill; Kim, Hugh I.

In: Analytical chemistry, Vol. 86, No. 3, 04.02.2014, p. 1909-1916.

Research output: Contribution to journalArticle

Lee, Shin Jung C ; Lee, Jong Wha ; Choi, Tae Su ; Jin, Kyeong Sik ; Lee, Seonghwan ; Ban, Changill ; Kim, Hugh I. / Probing conformational change of intrinsically disordered α-synuclein to helical structures by distinctive regional interactions with lipid membranes. In: Analytical chemistry. 2014 ; Vol. 86, No. 3. pp. 1909-1916.
@article{93c873b1705c40f883e9d2f51b69a2a8,
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.",
author = "Lee, {Shin Jung C} and Lee, {Jong Wha} and Choi, {Tae Su} and Jin, {Kyeong Sik} and Seonghwan Lee and Changill Ban and Kim, {Hugh I.}",
year = "2014",
month = "2",
day = "4",
doi = "10.1021/ac404132g",
language = "English",
volume = "86",
pages = "1909--1916",
journal = "Industrial And Engineering Chemistry Analytical Edition",
issn = "0003-2700",
publisher = "American Chemical Society",
number = "3",

}

TY - JOUR

T1 - Probing conformational change of intrinsically disordered α-synuclein to helical structures by distinctive regional interactions with lipid membranes

AU - Lee, Shin Jung C

AU - Lee, Jong Wha

AU - Choi, Tae Su

AU - Jin, Kyeong Sik

AU - Lee, Seonghwan

AU - Ban, Changill

AU - Kim, Hugh I.

PY - 2014/2/4

Y1 - 2014/2/4

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84893536897&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84893536897&partnerID=8YFLogxK

U2 - 10.1021/ac404132g

DO - 10.1021/ac404132g

M3 - Article

VL - 86

SP - 1909

EP - 1916

JO - Industrial And Engineering Chemistry Analytical Edition

JF - Industrial And Engineering Chemistry Analytical Edition

SN - 0003-2700

IS - 3

ER -