A soluble α-synuclein construct forms a dynamic tetramer Academic Article uri icon

Overview

MeSH Major

  • Models, Molecular
  • Polymers
  • Protein Structure, Secondary
  • alpha-Synuclein

abstract

  • A heterologously expressed form of the human Parkinson disease-associated protein α-synuclein with a 10-residue N-terminal extension is shown to form a stable tetramer in the absence of lipid bilayers or micelles. Sequential NMR assignments, intramonomer nuclear Overhauser effects, and circular dichroism spectra are consistent with transient formation of α-helices in the first 100 N-terminal residues of the 140-residue α-synuclein sequence. Total phosphorus analysis indicates that phospholipids are not associated with the tetramer as isolated, and chemical cross-linking experiments confirm that the tetramer is the highest-order oligomer present at NMR sample concentrations. Image reconstruction from electron micrographs indicates that a symmetric oligomer is present, with three- or fourfold symmetry. Thermal unfolding experiments indicate that a hydrophobic core is present in the tetramer. A dynamic model for the tetramer structure is proposed, based on expected close association of the amphipathic central helices observed in the previously described micelle-associated "hairpin" structure of α-synuclein.

publication date

  • October 25, 2011

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3203798

Digital Object Identifier (DOI)

  • 10.1073/pnas.1113260108

PubMed ID

  • 22006323

Additional Document Info

start page

  • 17797

end page

  • 802

volume

  • 108

number

  • 43