Department of Physics and Astronomy, Michigan State University, East Lansing, Michigan 48824, USA.
J Biol Chem. 2012 Mar 16;287(12):9193-9. doi: 10.1074/jbc.M111.325548. Epub 2012 Jan 20.
α-Synuclein is a protein that is intrinsically disordered in vitro and prone to aggregation, particularly at high temperatures. In this work, we examined the ability of curcumin, a compound found in turmeric, to prevent aggregation of the protein. We found strong binding of curcumin to α-synuclein in the hydrophobic non-amyloid-β component region and complete inhibition of oligomers or fibrils. We also found that the reconfiguration rate within the unfolded protein was significantly increased at high temperatures. We conclude that α-synuclein is prone to aggregation because its reconfiguration rate is slow enough to expose hydrophobic residues on the same time scale that bimolecular association occurs. Curcumin rescues the protein from aggregation by increasing the reconfiguration rate into a faster regime.
α-突触核蛋白在体外是一种无规则卷曲的蛋白，容易聚集，特别是在高温下。在这项工作中，我们研究了姜黄素（一种在姜黄中发现的化合物）预防该蛋白聚集的能力。我们发现姜黄素与 α-突触核蛋白在疏水性非淀粉样β成分区域有很强的结合，完全抑制了寡聚物或原纤维的形成。我们还发现，在高温下，未折叠蛋白的重新配置速率显著增加。我们得出的结论是，α-突触核蛋白容易聚集，是因为其重新配置的速度足够慢，以至于在双分子缔合发生的同时，暴露疏水性残基。姜黄素通过增加重新配置速率进入更快的状态，从而挽救蛋白免于聚集。
