Semisynthetic, Site-Specific Ubiquitin Modification of α-Synuclein Reveals Differential Effects on Aggregation

Citations Over TimeTop 10% of 2012 papers

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.

Related Papers

• → The role of α-synuclein in neurodegenerative diseases(2004)201 cited
• → Site-Specific Perturbations of Alpha-Synuclein Fibril Structure by the Parkinson's Disease Associated Mutations A53T and E46K(2013)62 cited
• → Degradation of wild‐type alpha‐synuclein by a molecular chaperone leads to reduced aggregate formation(2004)9 cited
• → Lack of binding observed between human α-synuclein and Bcl-2 protein family(2001)8 cited
• → Interaction of Human α-Synuclein with VTI1B May Modulate Vesicle Trafficking(2012)1 cited