Compartmentation of protein folding in vivo:: sequestration of non-native polypeptide by the chaperonin-GimC system
Compartmentation of protein folding in vivo:: sequestration of non-native polypeptide by the chaperonin-GimC system
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DOI：
10.1093/emboj/18.1.75
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发表时间：
1999-01-04
期刊：
影响因子：
11.4
通讯作者：
Hartl, FU
中科院分区：
文献类型：
--
作者：
Siegers, K;Waldmann, T;Hartl, FU
蛋白质合成和分子伴侣辅助折叠在体内的功能耦合仍然在很大程度上未被探索。在这里，我们已经分析了在酵母中的肌动蛋白的分子伴侣独立的折叠途径，值得注意的是，过表达的异源分子伴侣蛋白的陷阱非天然多肽不干扰蛋白质折叠在胞质溶胶中，表示一个高层次的组织折叠反应。新合成的肌动蛋白避免了伴侣蛋白陷阱，并有效地从核糖体到内源性伴侣蛋白TRiC的通道。TRiC上的有效肌动蛋白折叠严重依赖于异源寡聚共分子伴侣GimC。通过与折叠中间体和TRiC相互作用，GimC加速肌动蛋白折叠至少5倍，并防止非天然蛋白从TRiC过早释放。我们提出TRiC和GimC形成一个整合的“折叠室”，其与翻译机制合作发挥作用。该隔室将新合成的肌动蛋白和其他聚集敏感性多肽与细胞溶质的拥挤大分子环境隔离，从而允许它们有效折叠。
The functional coupling of protein synthesis and chaperone-assisted folding in vivo has remained largely unexplored. Here we have analysed the chaperon-independent folding pathway of actin in yeast, Remarkably, overexpression of a heterologous chaperonin which traps non-native polypeptides does not interfere with protein folding in the cytosol, indicating a high-level organization of folding reactions. Newly synthesized actin avoids the chaperonin trap and is effectively channelled from the ribosome to the endogenous chaperonin TRiC. Efficient actin folding on TRiC is critically dependent on the hetero-oligomeric co-chaperone GimC. By interacting with folding intermediates and with TRiC, GimC accelerates actin folding at least 5-fold and prevents the premature release of nonnative protein from TRiC, We propose that TRiC and GimC form an integrated 'folding compartment' which functions in cooperation with the translation machinery. This compartment sequesters newly synthesized actin and other aggregation-sensitive polypeptides from the crowded macromolecular environment of the cytosol, thereby allowing their efficient folding.