The early events of alpha-synuclein oligomerization revealed by photo-induced cross-linking.
Assembly of alpha-synuclein (alpha-Syn) into neurotoxic oligomers and fibrils is an important pathogenic feature of Parkinson's disease. Studying the early events of alpha-Syn aggregation, such as oligomerization and nucleation, is indispensable to understanding the complicated process. Here, photo-induced cross-linking of unmodified proteins (PICUP) technique is applied to elucidate the early-stage oligomerization of alpha-Syn. Results show that alpha-Syn in solution exhibits a mixture of various species, including at least monomers, dimers and trimers. Aggregation of alpha-Syn probably originates from the dimeric and trimeric seeds. Furthermore, the N-terminal amphipathic region is proposed to be required for the oligomerization (dimerization and trimerization) process. This observation may extend our knowledge on the early events of alpha-Syn aggregation and the neurotoxic aggregation species.
Li
Hong-Tao
HT
Key Laboratory of Proteomics, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. hyhu@sibs.ac.cn
Lin
Xiao-Jing
XJ
Xie
Yuan-Yuan
YY
Hu
Hong-Yu
HY
D003432:Cross-Linking Reagents / Q000737:chemistry; D019281:Dimerization; D008027:Light; D009942:Organometallic Compounds / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry; D020836:Protein Structure, Quaternary; D051844:alpha-Synuclein / Q000737:chemistry* / Q000528:radiation effects*
D003432:Cross-Linking Reagents; D009942:Organometallic Compounds; D010446:Peptide Fragments; D051844:alpha-Synuclein; C415768:tris(2,2'-bipyridyl)ruthenium(II)