Refolding of substrates bound to small Hsps relies on a disaggregation reaction mediated most efficiently by ClpB/DnaK
Refolding of substrates bound to small Hsps relies on a disaggregation reaction mediated most efficiently by ClpB/DnaK
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DOI：
10.1074/jbc.m303587200
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发表时间：
2003-08-15
影响因子：
4.8
通讯作者：
Bukau, B
中科院分区：
文献类型：
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作者：
Mogk, A;Schlieker, C;Bukau, B
小分子热休克蛋白（Small heat shock proteins，sHsps）是一种广泛存在的分子伴侣蛋白，它能在体外与变性蛋白结合，从而促进变性蛋白的重折叠。这个重折叠过程的机制基础是不明确的。我们证明，从各种来源的sHsps复合基板不会自发释放。sHsp结合底物的解离和重折叠依赖于由DnaK系统介导的解聚反应，或者更有效地，由ClpB/DnaK介导的解聚反应。虽然DnaK系统单独适用于小的可溶性sHsp/底物复合物，但ClpB/DnaK介导的蛋白质重折叠对于掺入sHsp的大的不溶性蛋白质聚集体是最快的。这些条件反映了体内的情况，其中sHsps通常在热应激期间与不溶性蛋白质相关联。因此，我们提出，sHsp在细胞蛋白质质量控制中的功能是促进DnaK或ClpB/DnaK在严重热应激后形成的聚集蛋白的快速再溶解。
Small heat shock proteins (sHsps) are ubiquitous molecular chaperones that bind denatured proteins in vitro, thereby facilitating their subsequent refolding by ATP-dependent chaperones. The mechanistic basis of this refolding process is poorly defined. We demonstrate that substrates complexed to sHsps from various sources are not released spontaneously. Dissociation and refolding of sHsp bound substrates relies on a disaggregation reaction mediated by the DnaK system, or, more efficiently, by ClpB/DnaK. While the DnaK system alone works for small, soluble sHsp/substrate complexes, ClpB/DnaK-mediated protein refolding is fastest for large, insoluble protein aggregates with incorporated sHsps. Such conditions reflect the situation in vivo, where sHsps are usually associated with insoluble proteins during heat stress. We therefore propose that sHsp function in cellular protein quality control is to promote rapid resolubilization of aggregated proteins, formed upon severe heat stress, by DnaK or ClpB/DnaK.