Alpha-Synuclein Disease Mutations Are Structurally Defective and Locally Affect Membrane Binding

Marta Robotta; Julia Cattani; Juliana Cristina Martins; Vinod Subramaniam; Malte Drescher

doi:10.1021/jacs.6b05335

Alpha-Synuclein Disease Mutations Are Structurally Defective and Locally Affect Membrane Binding

Marta Robotta, Julia Cattani, Juliana Cristina Martins, Vinod Subramaniam, Malte Drescher

Research output: Contribution to Journal › Article › Academic › peer-review

43 Downloads (Pure)

Abstract

The intrinsically disordered human protein alpha-Synuclein (αS) has a prominent role in Parkinson's disease (PD) pathology. Several familial variants of αS are correlated with inherited PD. Disease mutations have been shown to have an impact on lipid membrane binding. Here, using electron paramagnetic resonance spectroscopy in combination with site-directed spin labeling, we show that familial PD-associated variants are structurally defective in membrane binding and alter the local binding properties of the protein.

Original language	English
Pages (from-to)	4254-4257
Number of pages	4
Journal	Journal of the American Chemical Society
Volume	139
Issue number	12
Early online date	16 Mar 2017
DOIs	https://doi.org/10.1021/jacs.6b05335
Publication status	Published - 29 Mar 2017

Funding

This work was supported by the Deutsche Forschungsgemeinschaft(SFB969 and DR 746/10-1), Ministry of Science, Research and the Arts of Baden-Wurttemberg (AZ: 33-7532.20/723) and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-Brazil (CNPq) (238576/2012-4). V. S. acknowledges support from Foundation for Fundamental Research on Matter (FOM), now NWO Physics, via program FP127.

Funders	Funder number
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-Brazil
Ministry of Science, Research and the Arts of Baden-Wurttemberg	33-7532.20/723
Deutsche Forschungsgemeinschaft	DR 746/10-1, SFB969
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	FP127
Foundation for Fundamental Research on Matter
Conselho Nacional de Desenvolvimento Científico e Tecnológico	238576/2012-4

Keywords

Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1021/jacs.6b05335

Alpha-Synuclein Disease Mutations Are Structurally Defective and Locally Affect Membrane BindingFinal published version, 979 KBLicence: Article 25fa Dutch Copyright Act

Persistent URL (handle)

Persistent link

Cite this

@article{561c13b6ab31408188e5f059845b111d,

title = "Alpha-Synuclein Disease Mutations Are Structurally Defective and Locally Affect Membrane Binding",

abstract = "The intrinsically disordered human protein alpha-Synuclein (αS) has a prominent role in Parkinson's disease (PD) pathology. Several familial variants of αS are correlated with inherited PD. Disease mutations have been shown to have an impact on lipid membrane binding. Here, using electron paramagnetic resonance spectroscopy in combination with site-directed spin labeling, we show that familial PD-associated variants are structurally defective in membrane binding and alter the local binding properties of the protein.",

keywords = "Journal Article",

author = "Marta Robotta and Julia Cattani and Martins, {Juliana Cristina} and Vinod Subramaniam and Malte Drescher",

year = "2017",

month = mar,

day = "29",

doi = "10.1021/jacs.6b05335",

language = "English",

volume = "139",

pages = "4254--4257",

journal = "Journal of the American Chemical Society",

issn = "0002-7863",

publisher = "American Chemical Society",

number = "12",

}

TY - JOUR

T1 - Alpha-Synuclein Disease Mutations Are Structurally Defective and Locally Affect Membrane Binding

AU - Robotta, Marta

AU - Cattani, Julia

AU - Martins, Juliana Cristina

AU - Subramaniam, Vinod

AU - Drescher, Malte

PY - 2017/3/29

Y1 - 2017/3/29

N2 - The intrinsically disordered human protein alpha-Synuclein (αS) has a prominent role in Parkinson's disease (PD) pathology. Several familial variants of αS are correlated with inherited PD. Disease mutations have been shown to have an impact on lipid membrane binding. Here, using electron paramagnetic resonance spectroscopy in combination with site-directed spin labeling, we show that familial PD-associated variants are structurally defective in membrane binding and alter the local binding properties of the protein.

AB - The intrinsically disordered human protein alpha-Synuclein (αS) has a prominent role in Parkinson's disease (PD) pathology. Several familial variants of αS are correlated with inherited PD. Disease mutations have been shown to have an impact on lipid membrane binding. Here, using electron paramagnetic resonance spectroscopy in combination with site-directed spin labeling, we show that familial PD-associated variants are structurally defective in membrane binding and alter the local binding properties of the protein.

KW - Journal Article

UR - http://www.scopus.com/inward/record.url?scp=85016422851&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85016422851&partnerID=8YFLogxK

U2 - 10.1021/jacs.6b05335

DO - 10.1021/jacs.6b05335

M3 - Article

C2 - 28298083

SN - 0002-7863

VL - 139

SP - 4254

EP - 4257

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 12

ER -

Alpha-Synuclein Disease Mutations Are Structurally Defective and Locally Affect Membrane Binding

Abstract

Funding

Keywords

UN SDGs

Access to Document

Persistent URL (handle)

Other files and links

Fingerprint

Cite this