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Comparison of the Unfolding and Oligomerization of Human Prion Protein under acidic and neutral environments by Molecular Dynamics Simulations
Chemical Physics Letters ( IF 2.8 ) Pub Date : 2018-07-06 , DOI: 10.1016/j.cplett.2018.07.014
Ya Gao , Tong Zhu , Chaomin Zhang , John Z.H. Zhang , Ye Mei

Aggregation of the misfolded scrapie prion protein (PrPSc) is known to cause neurodegenerative diseases. In this paper, we have investigated the stability of PrPC by combining coarse-grained model and all-atom molecular simulations. Our results show that the unfolding of PrPC starts from the opening of the folded domain with α1 moving away from α2α3 domain, and then arrives at a metastable intermediate, and forms a more stable dimer complex in the end. This work unravels the mechanism of the early stage of conformational conversion and dimerization of prion protein and provides significant hints for the development of anti-prion therapeutics.



中文翻译:

分子动力学模拟比较酸性和中性环境下人Pri蛋白的解折叠和低聚

折叠错误的瘙痒病pr病毒蛋白(PrP Sc)的聚集已知会引起神经退行性疾病。在本文中,我们通过结合粗粒度模型和全原子分子模拟研究了PrP C的稳定性。我们的结果表明,PrP C的展开从折叠结构域的打开开始,α1离开 α2个α3域,然后到达一个亚稳的中间体,并最终形成一个更稳定的二聚体复合物。这项工作揭示了病毒蛋白构象转化和二聚化早期阶段的机制,并为抗-病毒疗法的发展提供了重要的提示。

更新日期:2018-07-08
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