A Stable Lipid-Induced Aggregate of alpha-Synuclein

Drescher, Malte; Rooijen, Bart D. van; Veldhuis, Gertjan; Subramaniam, Vinod; Huber, Martina

A Stable Lipid-Induced Aggregate of alpha-Synuclein

Dateien

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Datum

2010

Autor:innen

Drescher, Malte

Rooijen, Bart D. van

Veldhuis, Gertjan

Subramaniam, Vinod

Huber, Martina

Open Access-Veröffentlichung

Open Access Green

Sammlungen

Chemie
Zukunftskolleg

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Journal of the American Chemical Society. 2010, 132(12), pp. 4080-4082. ISSN 0002-7863. eISSN 1520-5126. Available under: doi: 10.1021/ja909247j

Zusammenfassung

The Parkinson’s disease-related protein α-Synuclein (αS) is a 140 residue intrinsically disordered protein. Its membrane-binding properties are thought to be relevant for its physiological or pathologic activity. Here, the interaction of αS with POPG [1-Palmitoyl-2-Oleoyl-sn-Glycero-3-(Phosphorac-(1-glycerol))] small unilamellar vesicles (SUVs) is investigated by spin-label EPR using double electron−electron resonance (DEER). Intermolecular distances between four single mutants reveal that well-defined aggregates are formed. The data suggest a coexistence of two dimer structures with main interactions in the helix 2, encompassing residues 50−100. Previously, the horseshoe conformation was detected by intramolecular restraints obtained by DEER on αS double mutants (Drescher et al. J. Am. Chem. Soc. 2008, 130, 7796). The present study suggests that interdigitation of two monomers in the aggregate fills the void between the two helices of each of the monomers thus providing a rationale for the horseshoe structure. This aggregate is lipid induced and affects the structure of the POPG SUVs, which become leaky and diminish in size upon contact with αS suggesting a possible origin of conflicting results in the recent literature (Jao et al. Proc. Natl. Acad. Sci. U.S.A. 2008, 105 (50), 19666; Georgieva et al. J. Am. Chem. Soc. 2008, 130 (39), 12856; Bortolus et al. J. Am. Chem. Soc. 2008, 130, 6690).

Fachgebiet (DDC)

540 Chemie

Zitieren

ISO 690

DRESCHER, Malte, Bart D. van ROOIJEN, Gertjan VELDHUIS, Vinod SUBRAMANIAM, Martina HUBER, 2010. A Stable Lipid-Induced Aggregate of alpha-Synuclein. In: Journal of the American Chemical Society. 2010, 132(12), pp. 4080-4082. ISSN 0002-7863. eISSN 1520-5126. Available under: doi: 10.1021/ja909247j

BibTex

@article{Drescher2010Stabl-13613,
  year={2010},
  doi={10.1021/ja909247j},
  title={A Stable Lipid-Induced Aggregate of alpha-Synuclein},
  number={12},
  volume={132},
  issn={0002-7863},
  journal={Journal of the American Chemical Society},
  pages={4080--4082},
  author={Drescher, Malte and Rooijen, Bart D. van and Veldhuis, Gertjan and Subramaniam, Vinod and Huber, Martina}
}

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