Systems analyses reveal two chaperone networks with distinct functions in eukaryotic cells
Systems analyses reveal two chaperone networks with distinct functions in eukaryotic cells
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DOI：
10.1016/j.cell.2005.11.039
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发表时间：
2006-01-13
期刊：
影响因子：
64.5
通讯作者：
Frydman, J
中科院分区：
文献类型：
--
作者：
Albanèse, V;Yam, AYW;Frydman, J
分子伴侣有助于新翻译和应激变性蛋白质的折叠。在原核生物中，重叠的伴侣蛋白组介导这两个过程。相反，我们发现真核生物进化出独特的伴侣网络来执行这些功能。基因组和功能分析表明，除了压力诱导的分子伴侣，保护细胞蛋白质组免受压力，真核生物包含一个压力抑制分子伴侣网络，致力于蛋白质的生物合成。这些应激抑制的分子伴侣在转录、功能和物理上与翻译装置相连，并与从核糖体出现的新生多肽相关。与从头蛋白质折叠中的功能一致，与蛋白质合成相关的分子伴侣网络的损伤使得细胞在蛋白质合成的背景下对错误折叠敏感，但在环境应激的背景下不敏感。一个连接蛋白伴侣网络的出现可能是复杂的共翻译折叠过程的基础，这是真核细胞中较大的多结构域蛋白质进化所必需的。
Molecular chaperones assist the folding of newly translated and stress-denatured proteins. In prokaryotes, overlapping sets of chaperones mediate both processes. In contrast, we find that eukaryotes evolved distinct chaperone networks to carry out these functions. Genomic and functional analyses indicate that in addition to stress-inducible chaperones that protect the cellular proteome from stress, eukaryotes contain a stress-repressed chaperone network that is dedicated to protein biogenesis. These stress-repressed chaperones are transcriptionally, functionally, and physically linked to the translational apparatus and associate with nascent polypeptides emerging from the ribosome. Consistent with a function in de novo protein folding, impairment of the translation-linked chaperone network renders cells sensitive to misfolding in the context of protein synthesis but not in the context of environmental stress. The emergence of a translation-linked chaperone network likely underlies the elaborate cotranslational folding process necessary for the evolution of larger multidomain proteins characteristic of eukaryotic cells.