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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。
Prions are a new type of causative agent that causes many neurodegenerative diseases with a new pathogenic mechanism. Its pathogenicity is primarily due to the conformational transition of PrPC to PrPSc. To investigate the mechanism of the conformational changes of PrP in the PrPSc transition to PrPSc, we calculated the solvent accessibility of amino acid residues of human natural PrP and different single residue mutants (such as M166V, S170N, E200K and R220K) Structural overlap simulation and RMS bias analysis of native PrP molecules and their mutants were also performed. The results showed that due to the mutation of single residue at position 166, the local structure of PrP mutant and native protein appeared to be greatly different, which caused some changes of solvent accessible surface area of some residues and some residues changed them Position, but also affects the distribution of charges on the surface of the protein, these changes are to better adapt to the secondary interaction of the local environment. Analysis shows that PrP and globulin in nature have some differences, indicating that the PrP molecule is not a stable globulin structure, just a folding intermediate.