SUN Gui-hong, GUO Ming-xiong, GONG Rui, MEI Fang-hua, WAN Yun-lian, XIAO Geng-fu and TIAN Bo. Solvent Accessibility and Computer Modeling Analysis on the Native and the Mutants of Human Prion Protein[J]. Virologica Sinica, 2004, 19(2): 158-162.
Citation: SUN Gui-hong, GUO Ming-xiong, GONG Rui, MEI Fang-hua, WAN Yun-lian, XIAO Geng-fu, TIAN Bo. Solvent Accessibility and Computer Modeling Analysis on the Native and the Mutants of Human Prion Protein .VIROLOGICA SINICA, 2004, 19(2) : 158-162.

人朊病毒蛋白及其突变体的溶剂可及性和模拟分析*

  • 通讯作者: 肖庚富, 
  • 朊病毒是一种全新类型的致病因子,以一种全新的致病机制造成许多神经退化性疾病。它的致病性主要由于PrPC向PrPSc构象转变而造成。为了探讨PrPC向PrPSc转变过程中PrP分子构象变化的机制, 我们计算分析了人天然PrP分子及不同的单残基突变体(如M166V,S170N,E200K和R220K)的氨基酸残基溶剂可及性, 并对天然PrP分子及其突变体进行了结构重叠模拟和RMS偏量分析。结果表明:由于166位等单个残基的突变, 造成PrP突变体与天然蛋白的局部结构出现较大差别, 使得部分残基的溶剂可及表面积发生了较大变化, 并且部分残基改变了它们的位置, 同时也影响蛋白质表面的电荷分布, 这些改变是为了更好地适应次级相互作用的局部环境。分析表明PrP与一般球蛋白在性质上有一定的差异, 说明PrP分子并不是一种稳定的球蛋白结构, 只是一种折叠中间物。

Solvent Accessibility and Computer Modeling Analysis on the Native and the Mutants of Human Prion Protein

  • Corresponding author: XIAO Geng-fu, 
  • Prions are unprecedented infectious pathogens that cause a group of invariably fatal neurodegenerative diseases by an entirely novel mechanism. Prion diseases result from abnormally folded isoform (PrPSc) of the cellular prion protein (PrPC). In order to investigate the molecular mechanisms of the conversion of PrPC into PrPSc, we calculated the solvent accessibility of amino acid residues in native HuPrP and its single amino acid residual mutants, such as M166V, S170N, E200K and R220K. We also modeled structural overlaps of native PrP and its mutants, analyzed their root mean squared (RMS) deviations. Results showed that the local conformation is intensely different between the native PrP and its mutants owing to the variation of M166V etc. The single amino acid residual mutant not only lead to great changes of the solvent accessible surface area (SASA) and positions of part residues, but also influence the distribution of the protein surface charges. These changes may adapt well to the local surroundings of the secondary interactions. We also conclude that there is some difference between PrP and normal globular protein, indicating that PrP can’t form a stable globular protein; it’s only a folding intermediate.

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    通讯作者: 陈斌, bchen63@163.com
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      沈阳化工大学材料科学与工程学院 沈阳 110142

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    Solvent Accessibility and Computer Modeling Analysis on the Native and the Mutants of Human Prion Protein

      Corresponding author: XIAO Geng-fu,
    • 1. 1. College of Life Science, Wuhan University, Wuhan 430072, China
    • 2. Medical College, Wuhan University, Wuhan 430071, China
    • 3. Computer Room, Hubei College of Traditional Chinese Medicine, Wuhan 430061, China

    Abstract: Prions are unprecedented infectious pathogens that cause a group of invariably fatal neurodegenerative diseases by an entirely novel mechanism. Prion diseases result from abnormally folded isoform (PrPSc) of the cellular prion protein (PrPC). In order to investigate the molecular mechanisms of the conversion of PrPC into PrPSc, we calculated the solvent accessibility of amino acid residues in native HuPrP and its single amino acid residual mutants, such as M166V, S170N, E200K and R220K. We also modeled structural overlaps of native PrP and its mutants, analyzed their root mean squared (RMS) deviations. Results showed that the local conformation is intensely different between the native PrP and its mutants owing to the variation of M166V etc. The single amino acid residual mutant not only lead to great changes of the solvent accessible surface area (SASA) and positions of part residues, but also influence the distribution of the protein surface charges. These changes may adapt well to the local surroundings of the secondary interactions. We also conclude that there is some difference between PrP and normal globular protein, indicating that PrP can’t form a stable globular protein; it’s only a folding intermediate.

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