The yeast prion [PSI+] is a self-propagating amyloid of the translation termination factor, Sup35p. For known pathogenic prions, such as [PSI+], a single protein can form an array of different amyloid structures (prion variants) each stably inherited and with differing biological properties. The ribosome-associated chaperones, Ssb1/2p (Hsp70s), and RAC (Zuo1p (Hsp40) and Ssz1p (Hsp70)), enhance de novo protein folding by protecting nascent polypeptide chains from misfolding and maintain translational fidelity by involvement in translation termination. Ssb1/2p and RAC chaperones were previously found to inhibit [PSI+] prion generation. We find that most [PSI+] variants arising in the absence of each chaperone were cured by restoring normal levels of that protein. [PSI+] variants hypersensitive to Ssb1/2p have distinguishable biological properties from those hypersensitive to Zuo1p or Ssz1p. The elevated [PSI+] generation frequency in each deletion strain is not due to an altered [PIN+], another prion that primes [PSI+] generation. [PSI+] prion generation/propagation may be inhibited by Ssb1/2/RAC chaperones by ensuring proper folding of nascent Sup35p, thus preventing its joining amyloid fibers. Alternatively, the effect of RAC/Ssb mutations on translation termination and the absence of an effect on the [URE3] prion suggest an effect on the mature Sup35p such that it does not readily join amyloid filaments. Ssz1p is degraded in zuo1Δ [psi-] cells, but not if the cells carry any of several [PSI+] variants. Our results imply that prions arise more frequently than had been thought but the cell has evolved exquisite antiprion systems that rapidly eliminate most variants.

酵母朊病毒 [PSI+] 是翻译终止因子 Sup35p 的自我增殖淀粉样蛋白。对于已知的致病性朊病毒，例如 [PSI+]，单个蛋白质可以形成一系列不同的淀粉样蛋白结构（朊病毒变体），每个结构稳定遗传并具有不同的生物学特性。核糖体相关的伴侣蛋白 Ssb1/2p (Hsp70s) 和 RAC (Zuo1p (Hsp40) 和 Ssz1p (Hsp70)) 通过保护新生多肽链不发生错误折叠来增强从头蛋白质折叠，并通过参与翻译终止来维持翻译保真度。先前发现 Ssb1/2p 和 RAC 伴侣可抑制 [PSI+] 朊病毒的产生。我们发现，在缺乏每个伴侣的情况下出现的大多数 [PSI+] 变体通过恢复该蛋白质的正常水平而得到治愈。[PSI+] 对 Ssb1/2p 过敏的变体具有与对 Zuo1p 或 Ssz1p 过敏的不同的生物学特性。每个缺失菌株中升高的 [PSI+] 生成频率不是由于 [PIN+] 的改变，另一种引发 [PSI+] 生成的朊病毒。[PSI+] 朊病毒的产生/传播可能会被 Ssb1/2/RAC 伴侣通过确保新生 Sup35p 的正确折叠来抑制，从而阻止其连接淀粉样蛋白纤维。或者，RAC/Ssb 突变对翻译终止的影响以及对 [URE3] 朊病毒没有影响表明对成熟的 Sup35p 有影响，因此它不容易加入淀粉样蛋白细丝。ssz1p 在 另一种引发 [PSI+] 生成的朊病毒。[PSI+] 朊病毒的产生/传播可能会被 Ssb1/2/RAC 伴侣通过确保新生 Sup35p 的正确折叠来抑制，从而阻止其连接淀粉样蛋白纤维。或者，RAC/Ssb 突变对翻译终止的影响以及对 [URE3] 朊病毒没有影响表明对成熟的 Sup35p 有影响，因此它不容易加入淀粉样蛋白细丝。ssz1p 在 另一种引发 [PSI+] 生成的朊病毒。[PSI+] 朊病毒的产生/传播可能会被 Ssb1/2/RAC 伴侣通过确保新生 Sup35p 的正确折叠来抑制，从而阻止其连接淀粉样蛋白纤维。或者，RAC/Ssb 突变对翻译终止的影响以及对 [URE3] 朊病毒没有影响表明对成熟的 Sup35p 有影响，因此它不容易加入淀粉样蛋白细丝。ssz1p 在zuo1 Δ [psi-] 细胞，但如果细胞携带几种 [PSI+] 变体中的任何一种，则不会。我们的结果表明，朊病毒出现的频率比想象的要高，但细胞已经进化出精致的抗朊病毒系统，可以迅速消除大多数变体。