Display Settings:

Format

Send to:

Choose Destination
Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):17797-802. doi: 10.1073/pnas.1113260108. Epub 2011 Oct 17.

A soluble α-synuclein construct forms a dynamic tetramer.

Author information

  • 1Department of Biochemistry and Molecular Biology, and Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

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.

PMID:
22006323
[PubMed - indexed for MEDLINE]
PMCID:
PMC3203798
Free PMC Article

Images from this publication.See all images (4)Free text

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk