Journal article
A soluble α-synuclein construct forms a dynamic tetramer
Proceedings of the National Academy of Sciences - PNAS, Vol.108(43), pp.17797-17802
10/25/2011
Handle:
https://hdl.handle.net/2376/110947
PMCID: PMC3203798
PMID: 22006323
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.
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Details
- Title
- A soluble α-synuclein construct forms a dynamic tetramer
- Creators
- Wei Wang - Indiana University School of MedicineIva Perovic - Department of Chemistry and Rosenstiel Basic Medical Sciences Research CenterJohnathan Chittuluru - Department of Cell BiologyAlice Kaganovich - Laboratory of NeurogeneticsLinh T. T Nguyen - Department of Biochemistry and Molecular Biology, andJingling Liao - Department of Biochemistry and Molecular Biology, andJared R Auclair - Department of Chemistry and Rosenstiel Basic Medical Sciences Research CenterDerrick Johnson - Department of Biochemistry and Molecular Biology, andAnuradha Landeru - Department of Biochemistry and Molecular Biology, andAlana K Simorellis - Department of Chemistry and Biochemistry and Rosenstiel Basic Medical Sciences Research Center, andShulin Ju - Department of Chemistry and Biochemistry and Rosenstiel Basic Medical Sciences Research Center, andMark R Cookson - Laboratory of NeurogeneticsFrancisco J Asturias - Department of Cell BiologyJeffrey N Agar - Department of Chemistry and Rosenstiel Basic Medical Sciences Research CenterBrian N Webb - Department of ChemistryChulHee Kang - Department of ChemistryDagmar Ringe - Department of Chemistry and Biochemistry and Rosenstiel Basic Medical Sciences Research Center, andGregory A Petsko - Department of Chemistry and Biochemistry and Rosenstiel Basic Medical Sciences Research Center, andThomas C Pochapsky - Department of Chemistry and Biochemistry and Rosenstiel Basic Medical Sciences Research Center, andQuyen Q Hoang - Department of Biochemistry and Molecular Biology, and
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.108(43), pp.17797-17802
- Academic Unit
- Department of Chemistry
- Publisher
- National Academy of Sciences
- Number of pages
- 6
- Identifiers
- 99900547274301842
- Language
- English
- Resource Type
- Journal article