title: Semisynthetic, site-specific ubiquitin modification of α-synuclein reveals differential effects on aggregation.
abstract: The process of neurodegeneration in Parkinson's Disease is intimately associated with the aggregation of the protein α-synuclein into toxic oligomers and fibrils. Interestingly, many of these protein aggregates are found to be post-translationally modified by ubiquitin at several different lysine residues. However, the inability to generate homogeneously ubiquitin modified α-synuclein at each site has prevented the understanding of the specific biochemical consequences. We have used protein semisynthesis to generate nine site-specifically ubiquitin modified α-synuclein derivatives and have demonstrated that different ubiquitination sites have differential effects on α-synuclein aggregation.
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, California 90089, United States.
authors.forename: Franziska
authors.initials: F
authors.lastname: Meier
authors.forename: Tharindumala
authors.initials: T
authors.lastname: Abeywardana
authors.forename: Abhinav
authors.initials: A
authors.lastname: Dhall
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Marotta
authors.forename: Jobin
authors.initials: J
authors.lastname: Varkey
authors.forename: Ralf
authors.initials: R
authors.lastname: Langen
authors.forename: Champak
authors.initials: C
authors.lastname: Chatterjee
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Pratt
mesh_terms: D000595:Amino Acid Sequence; D004220:Disulfides / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010300:Parkinson Disease / Q000378:metabolism; D011487:Protein Conformation; D025801:Ubiquitin / Q000737:chemistry* / Q000378:metabolism; D054875:Ubiquitination; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004220:Disulfides; D025801:Ubiquitin; D051844:alpha-Synuclein