朊蛋白淀粉样蛋白:从PrP聚合物中分离痒病传染性。

H. Wille, M. Baldwin, F. Cohen, S. DeArmond, S. Prusiner
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引用次数: 8

摘要

朊病毒蛋白(PrP)在细胞异构体(PrPc)转化为痒病蛋白(PrPSc)时发生了深刻的构象变化。有限的PrPSc蛋白水解产生PrP27-30,它很容易聚合成淀粉样蛋白。为了研究PrP淀粉样蛋白的结构,我们使用了干扰蛋白质构象的有机溶剂。1,1,1,3,3,3-六氟-2-丙醇(HFIP)可以促进α -螺旋的形成,改变棒状PrP淀粉样蛋白的超微结构,产生具有更规则亚结构的扁平带。随着HFIP浓度的增加,PrP27-30的β -sheet含量、蛋白酶K抗性和朊病毒感染性降低。HFIP可逆地降低了刚果红染料与杆状细胞的结合,而朊病毒的传染性失活是不可逆的。与10% HFIP相比,1,1,1-三氟-2-丙醇(TFIP)没有灭活朊病毒的感染性,但与HFIP相似,TFIP确实改变了杆状体的形态并消除了刚果红结合。我们的研究将朊病毒的感染性从PrP27-30的淀粉样蛋白特性中分离出来,并强调了朊病毒的感染性对PrPSc构象的依赖性。我们的研究结果还表明,朊病毒感染性所需的特异性-富β -薄片结构与淀粉样蛋白形成所需的结构不同。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Prion protein amyloid: separation of scrapie infectivity from PrP polymers.
The prion protein (PrP) undergoes a profound conformational change when the cellular isoform (PrPc) is converted into the scrapie form (PrPSc). Limited proteolysis of PrPSc produces PrP27-30 which readily polymerizes into amyloid. To study the structure of PrP amyloid, we employed organic solvents that perturb protein conformation. 1,1,1,3,3,3-Hexafluoro-2-propanol (HFIP), which promotes alpha-helix formation, modified the ultrastructure of rod-shaped PrP amyloids, producing flattened ribbons with a more regular substructure. As the concentration of HFIP was increased, the beta-sheet content and proteinase K resistance of PrP27-30 as well as prion infectivity diminished. HFIP reversibly decreased the binding of Congo red dye to the rods, whereas inactivation of prion infectivity was irreversible. In contrast to 10% HFIP, 1,1,1-trifluoro-2-propanol (TFIP) did not inactivate prion infectivity but, similarly to HFIP, TFIP did alter the morphology of the rods and abolished Congo red binding. Our studies separate prion infectivity from the amyloid properties of PrP27-30 and underscore the dependence of prion infectivity on PrPSc conformation. Our results also demonstrate that the specific beta-sheet-rich structures required for prion infectivity are different from those needed for amyloid formation.
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