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Preparation and Characterization of Stable α-Synuclein Lipoprotein Particles

Eichmann, Cédric and Campioni, Silvia and Kowal, Julia and Maslennikov, Innokentiy and Gerez, Juan and Liu, Xiaoxia and Verasdonck, Joeri and Nespovitaya, Nedezda and Choe, Senyon and Meier, Beat and Picotti, Paola and Rizo, Josep and Stahlberg, Henning and Riek, Roland. (2016) Preparation and Characterization of Stable α-Synuclein Lipoprotein Particles. Journal of Biological Chemistry, 291 (16). pp. 8516-8527.

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Abstract

Multiple neurodegenerative diseases are caused by the aggregation of the human α-Synuclein (α-Syn(6)) 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 approximately 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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Stahlberg)
UniBasel Contributors:Stahlberg, Henning
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Society for Biochemistry and Molecular Biology
ISSN:0021-9258
e-ISSN:1083-351X
Note:Publication type according to Uni Basel Research Database: Journal article -- The final publication is available at Journal of Biological Chemistry, see DOI link.
Language:English
Identification Number:
Last Modified:27 Sep 2017 10:11
Deposited On:29 Sep 2016 07:40

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