Lysine Acetylation Inhibits α-Synuclein Fibrillation

doi:10.11938/cjmr20160201

Abstract

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:

O482.53

ZHAI Zi-ning, WU Qiong, LI Cong-gang. Lysine Acetylation Inhibits α-Synuclein Fibrillation[J]. Chinese Journal of Magnetic Resonance, 2016, 33(2): 179-187.

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