title: A soluble α-synuclein construct forms a dynamic tetramer.
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.
authors: Department of Biochemistry and Molecular Biology, and Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors: Wei
authors: W
authors: Wang
authors: Iva
authors: I
authors: Perovic
authors: Johnathan
authors: J
authors: Chittuluru
authors: Alice
authors: A
authors: Kaganovich
authors: Linh T T
authors: LT
authors: Nguyen
authors: Jingling
authors: J
authors: Liao
authors: Jared R
authors: JR
authors: Auclair
authors: Derrick
authors: D
authors: Johnson
authors: Anuradha
authors: A
authors: Landeru
authors: Alana K
authors: AK
authors: Simorellis
authors: Shulin
authors: S
authors: Ju
authors: Mark R
authors: MR
authors: Cookson
authors: Francisco J
authors: FJ
authors: Asturias
authors: Jeffrey N
authors: JN
authors: Agar
authors: Brian N
authors: BN
authors: Webb
authors: Chulhee
authors: C
authors: Kang
authors: Dagmar
authors: D
authors: Ringe
authors: Gregory A
authors: GA
authors: Petsko
authors: Thomas C
authors: TC
authors: Pochapsky
authors: Quyen Q
authors: QQ
authors: Hoang
mesh_terms: D002942:Circular Dichroism; D006801:Humans; D008854:Microscopy, Electron; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011108:Polymers / Q000737:chemistry*; D017433:Protein Structure, Secondary; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: D011108:Polymers; D051844:alpha-Synuclein