Alpha-synuclein binds to the inner membrane of mitochondria in an α-helical conformation

Marta Robotta; Hanne R Gerding; Antonia Vogel; Karin Hauser; Stefan Schildknecht; Christiaan Karreman; Marcel Leist; Vinod Subramaniam; Malte Drescher

doi:10.1002/cbic.201402281

Alpha-synuclein binds to the inner membrane of mitochondria in an α-helical conformation

Marta Robotta, Hanne R Gerding, Antonia Vogel, Karin Hauser, Stefan Schildknecht, Christiaan Karreman, Marcel Leist, Vinod Subramaniam, Malte Drescher

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

Abstract

The human alpha-Synuclein (αS) protein is of significant interest because of its association with Parkinson's disease and related neurodegenerative disorders. The intrinsically disordered protein (140 amino acids) is characterized by the absence of a well-defined structure in solution. It displays remarkable conformational flexibility upon macromolecular interactions, and can associate with mitochondrial membranes. Site-directed spin-labeling in combination with electron paramagnetic resonance spectroscopy enabled us to study the local binding properties of αS on artificial membranes (mimicking the inner and outer mitochondrial membranes), and to evaluate the importance of cardiolipin in this interaction. With pulsed, two-frequency, double-electron electron paramagnetic resonance (DEER) approaches, we examined, to the best of our knowledge for the first time, the conformation of αS bound to isolated mitochondria.

Original language	English
Pages (from-to)	2499-502
Number of pages	4
Journal	ChemBioChem
Volume	15
Issue number	17
DOIs	https://doi.org/10.1002/cbic.201402281
Publication status	Published - 24 Nov 2014

Keywords

Binding Sites
HEK293 Cells
Humans
Mitochondria
Mitochondrial Membranes
Protein Conformation
alpha-Synuclein
Journal Article
Research Support, Non-U.S. Gov't

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title = "Alpha-synuclein binds to the inner membrane of mitochondria in an α-helical conformation",

abstract = "The human alpha-Synuclein (αS) protein is of significant interest because of its association with Parkinson's disease and related neurodegenerative disorders. The intrinsically disordered protein (140 amino acids) is characterized by the absence of a well-defined structure in solution. It displays remarkable conformational flexibility upon macromolecular interactions, and can associate with mitochondrial membranes. Site-directed spin-labeling in combination with electron paramagnetic resonance spectroscopy enabled us to study the local binding properties of αS on artificial membranes (mimicking the inner and outer mitochondrial membranes), and to evaluate the importance of cardiolipin in this interaction. With pulsed, two-frequency, double-electron electron paramagnetic resonance (DEER) approaches, we examined, to the best of our knowledge for the first time, the conformation of αS bound to isolated mitochondria.",

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author = "Marta Robotta and Gerding, {Hanne R} and Antonia Vogel and Karin Hauser and Stefan Schildknecht and Christiaan Karreman and Marcel Leist and Vinod Subramaniam and Malte Drescher",

note = "{\textcopyright} 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",

year = "2014",

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Alpha-synuclein binds to the inner membrane of mitochondria in an α-helical conformation. / Robotta, Marta; Gerding, Hanne R; Vogel, Antonia; Hauser, Karin; Schildknecht, Stefan; Karreman, Christiaan; Leist, Marcel; Subramaniam, Vinod; Drescher, Malte.

In: ChemBioChem, Vol. 15, No. 17, 24.11.2014, p. 2499-502.

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

TY - JOUR

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AU - Robotta, Marta

AU - Gerding, Hanne R

AU - Vogel, Antonia

AU - Hauser, Karin

AU - Schildknecht, Stefan

AU - Karreman, Christiaan

AU - Leist, Marcel

AU - Subramaniam, Vinod

AU - Drescher, Malte

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AB - The human alpha-Synuclein (αS) protein is of significant interest because of its association with Parkinson's disease and related neurodegenerative disorders. The intrinsically disordered protein (140 amino acids) is characterized by the absence of a well-defined structure in solution. It displays remarkable conformational flexibility upon macromolecular interactions, and can associate with mitochondrial membranes. Site-directed spin-labeling in combination with electron paramagnetic resonance spectroscopy enabled us to study the local binding properties of αS on artificial membranes (mimicking the inner and outer mitochondrial membranes), and to evaluate the importance of cardiolipin in this interaction. With pulsed, two-frequency, double-electron electron paramagnetic resonance (DEER) approaches, we examined, to the best of our knowledge for the first time, the conformation of αS bound to isolated mitochondria.

KW - Binding Sites

KW - HEK293 Cells

KW - Humans

KW - Mitochondria

KW - Mitochondrial Membranes

KW - Protein Conformation

KW - alpha-Synuclein

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

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DO - 10.1002/cbic.201402281

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SN - 1439-4227

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