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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, Josep; Stahlberg, Henning; Riek, Roland.
Afiliação
  • Eichmann C; From the Laboratory of Physical Chemistry and.
  • Campioni S; From the Laboratory of Physical Chemistry and.
  • Kowal J; Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel, Mattenstrasse 26, CH-4058 Basel, Switzerland.
  • Maslennikov I; Structural Biology Laboratory, The Salk Institute, La Jolla, California 92037 and.
  • Gerez J; Institute of Biochemistry, Swiss Federal Institute of Technology, ETH-Hönggerberg, CH-8093 Zürich, Switzerland.
  • Liu X; Department of Biophysics, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390.
  • Verasdonck J; From the Laboratory of Physical Chemistry and.
  • Nespovitaya N; From the Laboratory of Physical Chemistry and.
  • Choe S; Structural Biology Laboratory, The Salk Institute, La Jolla, California 92037 and.
  • Meier BH; From the Laboratory of Physical Chemistry and.
  • Picotti P; Institute of Biochemistry, Swiss Federal Institute of Technology, ETH-Hönggerberg, CH-8093 Zürich, Switzerland.
  • Rizo J; Department of Biophysics, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390.
  • Stahlberg H; Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel, Mattenstrasse 26, CH-4058 Basel, Switzerland.
  • Riek R; From the Laboratory of Physical Chemistry and Structural Biology Laboratory, The Salk Institute, La Jolla, California 92037 and roland.riek@phys.chem.ethz.ch.
J Biol Chem ; 291(16): 8516-27, 2016 Apr 15.
Article em En | MEDLINE | ID: mdl-26846854
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 ∼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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfolipídeos / Alfa-Sinucleína / Nanopartículas / Lipoproteínas HDL Limite: Humans Idioma: En Revista: J Biol Chem Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfolipídeos / Alfa-Sinucleína / Nanopartículas / Lipoproteínas HDL Limite: Humans Idioma: En Revista: J Biol Chem Ano de publicação: 2016 Tipo de documento: Article