Ubiquitination can change the structure of the α-synuclein amyloid fiber in a site selective fashion.

The formation of toxic amyloid aggregates is a common feature of many neurodegenerative diseases. An ever increasing number of biochemical and structural studies have demonstrated that not all amyloids of a given protein are equivalent, but rather that a single aggregating protein can form different amyloid structures or polymorphisms. Notably, different polymorphisms have also been shown to induce different amounts of pathology and toxicity in cells and in mice, suggesting that the structural differences may play important roles in disease. However, the features that might cause the formation of different polymorphisms in vivo are still being uncovered. The myriad posttranslational modifications that occur on several of the amyloid forming proteins, including the Parkinson’s disease causing protein α-synuclein, may be one such cause. Here, we explore whether the modification ubiquitination can induce structural changes in α-synuclein aggregates in vitro. To accomplish this we combine protein chemistry an...