title: Extent of inhibition of α-synuclein aggregation in vitro by SUMOylation is conjugation site- and SUMO isoform-selective.
abstract: α-Synuclein, the major aggregating protein in Parkinson's disease, can be modified by the small protein SUMO, indicating a potential role in disease. However, the effects of SUMOylation on α-synuclein aggregation remain controversial due to heterogeneous nature of the proteins previously investigated. Here we used protein semisynthesis to obtain homogeneously SUMOylated α-synuclein and discovered site- and isoform-dependent effects of SUMOylation on α-synuclein aggregation. Our results indicate that SUMOylation at K102 is a better inhibitor of aggregation than corresponding modification at K96 and SUMO1 modification, a better inhibitor than SUMO3.
authors.affiliation: Department of Chemistry and ‡Department of Molecular and Computational Biology, University of Southern California , Los Angeles, California 90089-0744, United States.
authors.forename: Tharindumala
authors.initials: T
authors.lastname: Abeywardana
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Pratt
mesh_terms: D066329:Protein Aggregates / Q000502:physiology*; D011485:Protein Binding / Q000502:physiology; D017433:Protein Structure, Secondary; D058207:Sumoylation / Q000502:physiology*; D051844:alpha-Synuclein / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*
chemical_list: D066329:Protein Aggregates; D051844:alpha-Synuclein