Extent of inhibition of α-synuclein aggregation in vitro by SUMOylation is conjugation site- and SUMO isoform-selective

Biochemistry. 2015 Feb 3;54(4):959-61. doi: 10.1021/bi501512m. Epub 2015 Jan 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Protein Aggregates / physiology*
  • Protein Binding / physiology
  • Protein Structure, Secondary
  • Sumoylation / physiology*
  • alpha-Synuclein / antagonists & inhibitors*
  • alpha-Synuclein / chemistry
  • alpha-Synuclein / metabolism*


  • Protein Aggregates
  • alpha-Synuclein