Chinese Journal of Magnetic Resonance >
Lysine Acetylation Inhibits α-Synuclein Fibrillation
Received date: 2015-05-13
Revised date: 2016-04-18
Online published: 2016-06-05
Supported by
Ministry of Science and Technology of China (2013CB910200);National Natural Science Foundation of China (21173258, 21120102038 and 21221064).
Fibrils of intrinsically disordered protein α-synuclein (α-syn) are hallmarks of Parkinson's disease. Electrostatic interactions are known to contribute significantly on α-syn aggregation. Here we studied how α-syn conformation and fibrillation were affected by changing the net charge of the protein via acetylation of lysine side chains. NMR spectroscopy results showed that lysine-acetylated α-syn remained disordered, and showed a more extended conformation, relative to wild-type protein. Acetylation inhibited α-syn fibrillation, revealed by thioflavin (ThT) fluorescence assay. The N- and C-terminals of the acetylated protein were highly negative charged, causing increased exposure of the non-amyloid-β component (NAC) region. It is proposed that, with the charge distribution in the acetylated protein, electrostatic repulsion, instead of hydrophobic effect, may contribute predominately to the aggregation. This charge-effect mechanism may constitute a new strategy to inhibit α-syn fibrillation.
Key words： liquid-state NMR; acetylation; fibrillation; α-synuclein
WU Qiong , LI Cong-gang , ZHAI Zi-ning . Lysine Acetylation Inhibits α-Synuclein Fibrillation[J]. Chinese Journal of Magnetic Resonance, 2016 , 33(2) : 179 -187 . DOI: 10.11938/cjmr20160201
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