A soluble alpha-synuclein construct forms a dynamic tetramer

作者：Wang Wei; Perovic Iva; Chittuluru Johnathan; Kaganovich Alice; Nguyen Linh T T; Liao Jingling; Auclair Jared R; Johnson Derrick; Landeru Anuradha; Simorellis Alana K; Ju Shulin; Cookson Mark R; Asturias Francisco J; Agar Jeffrey N; Webb Brian N; Kang ChulHee; Ringe Dagmar^*; Petsko Gregory A; Pochapsky Thomas C; Hoang Quyen Q

来源：Proceedings of the National Academy of Sciences of the United States of America, 2011, 108(43): 17797-17802.

DOI：10.1073/pnas.1113260108

• dynamic structure
• helical
• Parkinson's disease
• NMR
• heteronuclear single-quantum coherence

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

• 出版日期2011-10-25
• 单位NIH