Jones Gary W, Tuite Mick F
Department of Biology, National University of Ireland, Maynooth, Co. Kildare Ireland.
Bioessays. 2005 Aug;27(8):823-32. doi: 10.1002/bies.20267.
Newly made polypeptide chains require the help of molecular chaperones not only to rapidly reach their final three-dimensional forms, but also to unfold and then correctly refold them back to their biologically active form should they misfold. Most prions are an unusual type of protein that can exist in one of two stable conformations, one of which leads to formation of an infectious alternatively folded form. Studies in Baker's yeast (Saccharomyces cerevisiae) have revealed that prions can exploit the molecular chaperone machinery in the cell in order to ensure stable propagation of the infectious, aggregation-prone form. The disaggregation of yeast prion aggregates by molecular chaperones generates forms of the prion protein that can seed the protein polymerisation that underlies the prion propagation cycle. In this article, we review what we have learnt about the role of molecular chaperones in yeast prion propagation, describe a model that can explain the role of various classes of molecular chaperones and their co-chaperones, and speculate on the possible involvement of chaperones in the propagation of mammalian prions.
新合成的多肽链不仅需要分子伴侣的帮助才能迅速形成其最终的三维结构，而且如果它们发生错误折叠，还需要分子伴侣帮助它们展开，然后正确地重新折叠成具有生物活性的形式。大多数朊病毒是一种特殊类型的蛋白质，它可以以两种稳定构象之一存在，其中一种构象会导致形成具有传染性的另一种折叠形式。对面包酵母（酿酒酵母）的研究表明，朊病毒可以利用细胞中的分子伴侣机制，以确保具有传染性、易于聚集的形式稳定传播。分子伴侣对酵母朊病毒聚集体的解聚产生了朊病毒蛋白的形式，这些形式可以引发作为朊病毒传播循环基础的蛋白质聚合。在本文中，我们回顾了我们对分子伴侣在酵母朊病毒传播中的作用的了解，描述了一个可以解释各类分子伴侣及其共伴侣作用的模型，并推测了伴侣蛋白可能参与哺乳动物朊病毒的传播。
