Coordinated Hsp110 and Hsp104 Activities Power Protein Disaggregation in Saccharomyces cerevisiae.
Coordinated Hsp110 and Hsp104 Activities Power Protein Disaggregation in Saccharomyces cerevisiae.
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DOI：
10.1128/mcb.00027-17
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发表时间：
2017-06-01
影响因子：
5.3
通讯作者：
Andréasson C
中科院分区：
文献类型：
--
作者：
Kaimal JM;Kandasamy G;Gasser F;Andréasson C
蛋白质聚集与细胞应激密切相关，并且在衰老、疾病和细胞功能障碍期间加速。酵母细胞依靠 ATP 消耗分子伴侣 Hsp104 与 Hsp70 一起分解蛋白质。 Hsp110 是古老且丰富的分子伴侣，可与 Hsp70 形成复合物。在这里，我们提供的体内数据表明，酿酒酵母 Hsp110s Sse1 和 Sse2 对于 Hsp104 依赖性蛋白质解聚至关重要。热激后，Hsp110 和 Hsp70 复合物被募集到蛋白质聚集体中，并在解聚过程中与 Hsp104 一起发挥作用。在缺乏 Hsp110 的情况下，Hsp70 和 Hsp104 对聚集体的靶向作用受到损害，并且仍然到达聚集体的残留 Hsp104 无法分解。因此，需要 Hsp104 和 Hsp110 的协调活性来重新激活聚集的蛋白质。这些发现对于理解真核细胞如何管理错误折叠和淀粉样蛋白具有重要意义。
Protein aggregation is intimately associated with cellular stress and is accelerated during aging, disease, and cellular dysfunction. Yeast cells rely on the ATP-consuming chaperone Hsp104 to disaggregate proteins together with Hsp70. Hsp110s are ancient and abundant chaperones that form complexes with Hsp70. Here we provide in vivo data showing that the Saccharomyces cerevisiae Hsp110s Sse1 and Sse2 are essential for Hsp104-dependent protein disaggregation. Following heat shock, complexes of Hsp110 and Hsp70 are recruited to protein aggregates and function together with Hsp104 in the disaggregation process. In the absence of Hsp110, targeting of Hsp70 and Hsp104 to the aggregates is impaired, and the residual Hsp104 that still reaches the aggregates fails to disaggregate. Thus, coordinated activities of both Hsp104 and Hsp110 are required to reactivate aggregated proteins. These findings have important implications for the understanding of how eukaryotic cells manage misfolded and amyloid proteins.