A soluble ?-synuclein construct forms a dynamic tetramer.

ABSTRACT: A heterologously expressed form of the human Parkinson disease-associated protein ?-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 ?-helices in the first 100 N-terminal residues of the 140-residue ?-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 ?-synuclein.

SUBMITTER: Wang W 

PROVIDER: S-EPMC3203798 | biostudies-other | 2011 Oct

REPOSITORIES: biostudies-other