Johnson J L, Craig E A
Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, Wisconson 53706, USA.
J Cell Biol. 2001 Feb 19;152(4):851-6. doi: 10.1083/jcb.152.4.851.
In addition to regulating the ATPase cycle of Hsp70, a second critical role of Hsp40s has been proposed based on in vitro studies: binding to denatured protein substrates, followed by their presentation to Hsp70 for folding. However, the biological importance of this model is challenged by the fact that deletion of the substrate-binding domain of either of the two major Hsp40s of the yeast cytosol, Ydj1 and Sis1, leads to no severe defects, as long as regions necessary for Hsp70 interaction are retained. As an in vivo test of this model, requirements for viability were examined in a strain having deletions of both Hsp40 genes. Despite limited sequence similarity, the substrate-binding domain of either Sis1 or Ydj1 allowed cell growth, indicating they share overlapping essential functions. Furthermore, the substrate-binding domain must function in cis with a functional Hsp70-interacting domain. We conclude that the ability of cytosolic Hsp40s to bind unfolded protein substrates is an essential function in vivo.
除了调节Hsp70的ATP酶循环外，基于体外研究提出了Hsp40的第二个关键作用：与变性的蛋白质底物结合，然后将其呈递给Hsp70进行折叠。然而，该模型的生物学重要性受到以下事实的挑战：只要保留Hsp70相互作用所需的区域，酵母细胞质中两个主要Hsp40（Ydj1和Sis1）中任何一个的底物结合结构域的缺失都不会导致严重缺陷。作为该模型的体内测试，在一个缺失了两个Hsp40基因的菌株中检查了生存能力的要求。尽管序列相似性有限，但Sis1或Ydj1的底物结合结构域都能使细胞生长，表明它们具有重叠的基本功能。此外，底物结合结构域必须与功能性的Hsp70相互作用结构域顺式发挥作用。我们得出结论，细胞质Hsp40结合未折叠蛋白质底物的能力在体内是一项基本功能。
