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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Mechanism of regulation of Hsp70 chaperones by DnaJ cochaperones
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Mechanism of regulation of Hsp70 chaperones by DnaJ cochaperones

机译：DnaJ伴侣蛋白对Hsp70伴侣蛋白的调控机制

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Hsp70 chaperones assist a large variety of protein folding processes within the entire lifespan of proteins. Central to these activities is the regulation of Hsp70 by DnaJ cochaperones. DnaJ stimulates Hsp70 to hydrolyze ATP, a key step that closes its substrate-binding cavity and thus allows stable binding of substrate. We show that DnaJ stimulates ATP hydrolysis by Escherichia coli Hsp70, DnaJ, very efficiently to >1000-fold, but only if present at high (micro-molar) concentration. In contrast, the chaperone activity of DnaK in luciferase refolding was maximal at several hundredfold lower concentration of DnaJ. However, DnaJ was capable of maximally stimulating the DnaK ATPase even at this low concentration, provided that protein substrate was present, indicating synergistic action of DnaJ and substrate. Peptide substrates were poorly effective in this syncrgistic action. DnaJ action required binding of protein substrates to the central hydrophobic pocket of the substrate-binding cavity of DnaK, as evidenced by the reduced ability of DnaJ to stimulate ATP hydrolysis by a DnaK mutant with defects in substrate binding. At high concentrations, DnaJ itself served as substrate for DnaK in a process considered to be unphysiological. Mutant analysis furthermore revealed that DnaJ-mediated stimulation of ATP hydrolysis requires communi- cation between the ATPase and substrate-binding domains of DnaK. This mechanism thus allows DnaJ to tightly couple ATP hydrolysis by DnaK with substrate binding and to avoid jamming of the DnaK chaperone with peptides. It probably is conserved amo
机译：Hsp70分子伴侣在蛋白质的整个生命周期内协助多种蛋白质折叠过程。这些活动的中心是DnaJ伴侣蛋白对Hsp70的调节。 DnaJ刺激Hsp70水解ATP，这是关闭其底物结合腔并因此使底物稳定结合的关键步骤。我们显示DnaJ刺激大肠杆菌Hsp70，DnaJ ATP水解非常有效地> 1000倍，但仅当以高（微摩尔）浓度存在时才如此。相反，DnaK在萤光素酶重新折叠中的伴侣活性在DnaJ浓度降低几百倍时最大。然而，即使存在这种蛋白质底物，DnaJ仍能够最大程度地刺激DnaK ATPase，前提是存在蛋白质底物，表明DnaJ和底物具有协同作用。肽底物在这种协同作用中效果较差。 DnaJ的作用需要蛋白质底物与DnaK的底物结合腔的中央疏水口袋结合，这由DnaJ刺激DnaK突变体具有底物结合缺陷的刺激ATP水解的能力降低所证明。在高浓度下，DnaJ本身在被认为是非生理性的过程中充当DnaK的底物。突变分析进一步表明，DnaJ介导的ATP水解刺激需要ATPase与DnaK的底物结合域之间的通信。因此，该机制允许DnaJ将DnaK的ATP水解与底物结合紧密偶联，并避免DnaK分子伴侣与肽发生干扰。它可能是保守的amo

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