Medical Biotechnology Division, School of Biosciences and Technology, VIT University, Vellore, 632014, Tamil Nadu, India,
Cell Biochem Biophys. 2013;67(3):1307-18. doi: 10.1007/s12013-013-9663-z.
Polymorphisms in the human prion proteins lead to amino acid substitutions by the conversion of PrPC to PrPSc and amyloid formation, resulting in prion diseases such as familial Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker disease and fatal familial insomnia. Cation-π interaction is a non-covalent binding force that plays a significant role in protein stability. Here, we employ a novel approach by combining various in silico tools along with molecular dynamics simulation to provide structural and functional insight into the effect of mutation on the stability and activity of mutant prion proteins. We have investigated impressions of prevalent mutations including 1E1S, 1E1P, 1E1U, 1E1P, 1FKC and 2K1D on the human prion proteins and compared them with wild type. Structural analyses of the models were performed with the aid of molecular dynamics simulation methods. According to our results, frequently occurred mutations were observed in conserved sequences of human prion proteins and the most fluctuation values appear in the 2K1D mutant model at around helix 4 with residues ranging from 190 to 194. Our observations in this study could help to further understand the structural stability of prion proteins.
人类朊蛋白中的突变导致由 PrPC 向 PrPSc 的转换和淀粉样蛋白形成，从而导致朊病毒病，如家族性克雅氏病、格斯特曼-施特劳斯勒-舍因克病和致命性家族性失眠症。阳离子-π 相互作用是非共价键结合力，在蛋白质稳定性中起着重要作用。在这里，我们采用了一种新的方法，结合各种计算工具和分子动力学模拟，提供了结构和功能上的见解，了解突变对突变朊蛋白稳定性和活性的影响。我们研究了常见突变的影响，包括 1E1S、1E1P、1E1U、1E1P、1FKC 和 2K1D，这些突变在人类朊蛋白上，并将其与野生型进行了比较。使用分子动力学模拟方法对模型进行了结构分析。根据我们的结果，在人类朊蛋白的保守序列中观察到了频繁发生的突变，在 2K1D 突变体模型中，最明显的波动值出现在大约 4 号螺旋处，残基范围从 190 到 194。我们在这项研究中的观察结果可能有助于进一步了解朊蛋白的结构稳定性。
