Chinese Journal of Magnetic Resonance ›› 2016, Vol. 33 ›› Issue (2): 179-187.doi: 10.11938/cjmr20160201

Previous Articles     Next Articles

Lysine Acetylation Inhibits α-Synuclein Fibrillation

ZHAI Zi-ning1,2, WU Qiong1, LI Cong-gang1   

  1. 1. Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan(Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences), Wuhan 430071, China;
    2. University of Chinese Academy of Sciences, Beijing 100049, China
  • Received:2015-05-13 Revised:2016-04-18 Online:2016-06-05 Published:2016-06-05
  • Supported by:

    Ministry of Science and Technology of China (2013CB910200);National Natural Science Foundation of China (21173258, 21120102038 and 21221064).

Abstract:

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

CLC Number: