朊蛋白构象变化机制的初步探讨

Primary study on the mechanism of Prion protein's conformational changes

PrPc的二级结构发生变化导致部分α-螺旋转变为β-折叠而产生PrPsc,是导致神经退行性疾病的主要原因。蛋白质多肽链被氧化损伤为自由基,其二级结构发生变化,我们通过量子化学方法b3lyp/6-31g**计算出抽氢反应的焓变,以此确定氧化损伤的位点和构象的变化。计算发现,Cα-H键的断裂焓(BDE)较小,易抽氢,且形成的Cα-H自由基导致二面角Φ和Ψ发生明显的变化。这对于解释朊病毒的致病机理和错误折叠很有意义。

The transformation from PrP\+c to PrP\+\{sc\}caused by part of its αhelix changed into βsheet is the main cause of the neurodegenerative diseases Some residues of peptides were damaged by oxidization, and consequently they became protein radicals and their secondary structures were also influenced Bond dissociation enthalpies (BDE) of a set of peptide molecules were calculated using the method B3lyp/631g\+\{**\} of Gaussian program, with the purpose of investigating the damage sites and the conformation changes In conclusion, BDE of CαH is small and CαH is easily abstracted The formed CαH radicals lead to the variabilities of the dihedral angles Φ and Ψ, which is significant to elucidate the pathogenic mechanism and misfolding of Prion protein