title: The Involvement of His50 during Protein Disulfide Isomerase Binding Is Essential for Inhibiting α-Syn Fibril Formation.
abstract: An increased level of protein disulfide isomerase (PDI) is a protective response to various neurodegenerative disorders, including Parkinson's disease. Interaction of PDI with α-synuclein (α-Syn) has been shown to inhibit its aggregation. Here, we report the residue-specific mapping of binding of PDI to α-Syn. We demonstrate that α-Syn N-terminal residues V3-S9 and L38-V40 bind more strongly to PDI than residues V49-V52 do, as do C-terminal residues E123-M127 and D135-E137. In addition, we show that residue H50 is key in preventing aggregation. These findings improve our understanding of PDI-protected aggregation of wild-type α-Syn and its H50Q familial mutant.
authors.affiliation: Department of Bioscience and Bioengineering, Indian Institute of Technology Bombay , Mumbai 400076, India.
authors.forename: Priyatosh
authors.initials: P
authors.lastname: Ranjan
authors.affiliation: Department of Bioscience and Bioengineering, Indian Institute of Technology Bombay , Mumbai 400076, India.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Kumar
mesh_terms: D019943:Amino Acid Substitution; D000682:Amyloid / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D006639:Histidine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020125:Mutation, Missense; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism; D019704:Protein Disulfide-Isomerases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051844:alpha-Synuclein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D000682:Amyloid; C497604:SNCA protein, human; D051844:alpha-Synuclein; D006639:Histidine; D019704:Protein Disulfide-Isomerases