Baldwin M A, Pan K M, Nguyen J, Huang Z, Groth D, Serban A, Gasset M, Mehlhorn I, Fletterick R J, Cohen F E
Department of Neurology, University of California, San Francisco 94143-0518.
Philos Trans R Soc Lond B Biol Sci. 1994 Mar 29;343(1306):435-41. doi: 10.1098/rstb.1994.0041.
Although no chemical modifications have been found to distinguish the cellular prion protein PrPC from its infectious analogue PrPSc, spectroscopic methods such as Fourier transform infrared (FTIR) spectroscopy reveal a major conformational difference. PrPC is rich in alpha-helix but is devoid of beta-sheet, whereas PrPSc is high in beta-sheet. N-terminal truncation of PrPSc by limited proteolysis does not destroy infectivity but it increases the beta-sheet content and shifts the FTIR absorption to lower frequencies, typical of the cross beta-pleated sheets of amyloids. Thus the formation of PrPSc from PrPC involves a conformational transition in which one or more alpha-helical regions of the protein is converted to beta-sheet. This transition is mimicked by synthetic peptides, allowing predictions of domains of PrP involved in prion diseases.
尽管尚未发现有化学修饰能够区分细胞朊病毒蛋白PrPC与其具有传染性的类似物PrPSc，但诸如傅里叶变换红外（FTIR）光谱等光谱方法揭示了两者在构象上的主要差异。PrPC富含α-螺旋但缺乏β-折叠，而PrPSc则富含β-折叠。通过有限蛋白酶解对PrPSc进行N端截短不会破坏其传染性，但会增加β-折叠含量并使FTIR吸收向更低频率移动，这是淀粉样蛋白交叉β-折叠片的典型特征。因此，从PrPC形成PrPSc涉及构象转变，其中蛋白质的一个或多个α-螺旋区域转变为β-折叠。合成肽模拟了这种转变，从而能够预测与朊病毒疾病相关的PrP结构域。
