Abstract：
:The abnormal aggregation of α-synuclein (α-Syn) is closely associated with Parkinson's disease. Different post-translational modifications of α-Syn have been identified and contribute distinctly in α-Syn aggregation and cytotoxicity. Recently, α-Syn was reported to be N-terminally acetylated in cells, yet the functional implication of this modification, especially in α-Syn oligomerization, remains unclear. By using a solid-state nanopore system, we found that N-terminal acetylation can significantly decrease α-Syn oligomerization. Replica-exchange molecular dynamics simulations further revealed that addition of an acetyl group at the N-terminus disrupts intermolecular hydrogen bonds, which slows down the initial α-Syn oligomerization. Our finding highlights the essential role of N-terminal acetylation of α-Syn in preserving its native conformation against pathological aggregation.
journal_name
ACS Chem Neuroscijournal_title
ACS chemical neuroscienceauthors
Bu B,Tong X,Li D,Hu Y,He W,Zhao C,Hu R,Li X,Shao Y,Liu C,Zhao Q,Ji B,Diao Jdoi
10.1021/acschemneuro.7b00250subject
Has Abstractpub_date
2017-10-18 00:00:00pages
2145-2151issue
10issn
1948-7193journal_volume
8pub_type
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