Preparation and characterization of stable α-synuclein lipoprotein particles

Cédric Eichmann, Silvia Campioni, Julia Kowal, Innokentiy Maslennikov, Juan Gerez, Xiaoxia Liu, Joeri Verasdonck, Nadezhda Nespovitaya, Senyon Choe, Beat H. Meier, Paola Picotti, Jose Rizo-Rey, Henning Stahlberg, Roland Riek

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Multiple neurodegenerative diseases are caused by the aggregation of the human α-Synuclein (α-Syn) protein. α-Syn possesses high structural plasticity and the capability of interacting with membranes. Both features are not only essential for its physiological function but also play a role in the aggregation process. Recently it has been proposed that α-Syn is able to form lipid-protein particles reminiscent of high-density lipoproteins. Here, we present a method to obtain a stable and homogeneous population of nanometer-sized particles composed of α-Syn and anionic phospholipids. These particles are called α-Syn lipoprotein (nano) particles to indicate their relationship to high-density lipoproteins formed by human apolipoproteins in vivo and of in vitro self-assembling phospholipid bilayer nanodiscs. Structural investigations of the α-Syn lipoprotein particles by circular dichroism (CD) and magic angle solid-state nuclear magnetic resonance (MAS SS-NMR) spectroscopy establish that α-Syn adopts a helical secondary structure within these particles. Based on cryo-electron microscopy (cryo-EM) and dynamic light scattering (DLS) α-Syn lipoprotein particles have a defined size with a diameter of ∼23 nm. Chemical cross linking in combination with solution-state NMR and multiangle static light scattering (MALS) of α-Syn particles reveal a high order protein-lipid entity composed of α 8-10 α-Syn molecules. The close resemblance in size between cross-linked in vitro-derived α-Syn lipoprotein particles and a cross-linked species of endogenous α-Syn from SH-SY5Y human neuroblastoma cells indicates a potential functional relevance of α-Syn lipoprotein nanoparticles.

Original languageEnglish (US)
Pages (from-to)8516-8527
Number of pages12
JournalJournal of Biological Chemistry
Volume291
Issue number16
DOIs
StatePublished - Apr 15 2016

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Synucleins
Lipoproteins
HDL Lipoproteins
Phospholipids
Magnetic Resonance Spectroscopy
Agglomeration
Nuclear magnetic resonance
Neurodegenerative diseases
Cryoelectron Microscopy
Lipids
Proteins
Apolipoproteins
Population Dynamics
Dynamic light scattering
Circular Dichroism
Neuroblastoma
Neurodegenerative Diseases
Light scattering
Nanoparticles
Electron microscopy

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Eichmann, C., Campioni, S., Kowal, J., Maslennikov, I., Gerez, J., Liu, X., ... Riek, R. (2016). Preparation and characterization of stable α-synuclein lipoprotein particles. Journal of Biological Chemistry, 291(16), 8516-8527. https://doi.org/10.1074/jbc.M115.707968

Preparation and characterization of stable α-synuclein lipoprotein particles. / Eichmann, Cédric; Campioni, Silvia; Kowal, Julia; Maslennikov, Innokentiy; Gerez, Juan; Liu, Xiaoxia; Verasdonck, Joeri; Nespovitaya, Nadezhda; Choe, Senyon; Meier, Beat H.; Picotti, Paola; Rizo-Rey, Jose; Stahlberg, Henning; Riek, Roland.

In: Journal of Biological Chemistry, Vol. 291, No. 16, 15.04.2016, p. 8516-8527.

Research output: Contribution to journalArticle

Eichmann, C, Campioni, S, Kowal, J, Maslennikov, I, Gerez, J, Liu, X, Verasdonck, J, Nespovitaya, N, Choe, S, Meier, BH, Picotti, P, Rizo-Rey, J, Stahlberg, H & Riek, R 2016, 'Preparation and characterization of stable α-synuclein lipoprotein particles', Journal of Biological Chemistry, vol. 291, no. 16, pp. 8516-8527. https://doi.org/10.1074/jbc.M115.707968
Eichmann C, Campioni S, Kowal J, Maslennikov I, Gerez J, Liu X et al. Preparation and characterization of stable α-synuclein lipoprotein particles. Journal of Biological Chemistry. 2016 Apr 15;291(16):8516-8527. https://doi.org/10.1074/jbc.M115.707968
Eichmann, Cédric ; Campioni, Silvia ; Kowal, Julia ; Maslennikov, Innokentiy ; Gerez, Juan ; Liu, Xiaoxia ; Verasdonck, Joeri ; Nespovitaya, Nadezhda ; Choe, Senyon ; Meier, Beat H. ; Picotti, Paola ; Rizo-Rey, Jose ; Stahlberg, Henning ; Riek, Roland. / Preparation and characterization of stable α-synuclein lipoprotein particles. In: Journal of Biological Chemistry. 2016 ; Vol. 291, No. 16. pp. 8516-8527.
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AU - Liu, Xiaoxia

AU - Verasdonck, Joeri

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AU - Choe, Senyon

AU - Meier, Beat H.

AU - Picotti, Paola

AU - Rizo-Rey, Jose

AU - Stahlberg, Henning

AU - Riek, Roland

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