title: A four-amino acid linker between repeats in the α-synuclein sequence is important for fibril formation.
abstract: α-Synuclein is a 140-amino acid protein that can switch conformation among intrinsically disordered in solution, helical on a membrane, and β-sheet in amyloid fibrils. Using the fluorescence of single-tryptophan mutants, we determined the immersion of different regions of the protein into lipid membranes. Our results suggest the presence of a flexible break close to residues 52-55 between two helical domains. The four-amino acid linker is not necessary for membrane binding but is important for fibril formation. A deletion mutant lacking this linker aggregates extremely slowly and slightly inhibits wild-type aggregation, possibly by blocking the growing ends of fibrils.
authors.affiliation: Nanobiophysics, MESA+ Institute for Nanotechnology, and MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente , 7522 NB Enschede, The Netherlands.
authors.forename: Volodymyr V
authors.initials: VV
authors.lastname: Shvadchak
authors.forename: Vinod
authors.initials: V
authors.lastname: Subramaniam
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000235:genetics / Q000378:metabolism*; D000682:Amyloid / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005453:Fluorescence; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D014364:Tryptophan / Q000235:genetics / Q000378:metabolism; D051844:alpha-Synuclein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D000682:Amyloid; D051844:alpha-Synuclein; D014364:Tryptophan