The C-terminal domain of Hsp70 is responsible for paralog-specific regulation of ribonucleotide reductase.
The C-terminal domain of Hsp70 is responsible for paralog-specific regulation of ribonucleotide reductase.
复制标题
DOI：
10.1371/journal.pgen.1010079
复制
发表时间：
2022-04
期刊：
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
--
作者：
Hsp 70家族的分子伴侣是非常保守的，并在所有生物体中表达。在芽殖酵母中，细胞表达四种高度相似的胞质Hsp 70 Ssa 1、2、3和4，它们是由基因复制产生的。Ssa 1和2组成型表达，而Ssa 3和4诱导热休克。最近的证据表明，尽管它们的氨基酸相似，但这些Ssa在细胞中具有独特的作用。在这里，我们研究的相对重要性，Ssa 1 -4在调节的酶核糖核苷酸还原酶（RNR）。我们证明，细胞表达Ssa 3或Ssa 4作为其唯一的Ssa是妥协的，他们的耐DNA损伤剂和DNA损伤反应（DDR）调节转录的激活。此外，我们表明，稳态水平和稳定性的RNR小亚基Rnr 2和Rnr 4的Ssa 3或Ssa 4表达细胞中，减少Ssa-RNR相互作用的结果。在仅表达Ssa 3和4的细胞中，Hsp 70共伴侣Ydj 1和RNR之间的相互作用相应地降低。通过对Ssa 2/4结构域交换嵌合体的研究，我们确定Ssa的C-末端结构域是这种功能特异性的来源。综上所述，我们的工作表明，在调节C-末端序列变异介导的DNA复制的SSA旁系同源物的独特作用。细胞需要分子伴侣将蛋白质折叠成它们的活性构象。然而，一个主要的谜团是为什么细胞表达如此多的高度相关和明显冗余的Hsp 70旁系同源物。我们研究了四个Hsp 70旁系同源物在芽殖酵母（SSA 1，2，3和4）的核糖核苷酸还原酶（RNR复合物）的活性的作用。重要的是，我们证明了RNR亚基对Ssa 1和Ssa 2亚基的选择性，这是由共伴侣Ydj 1决定的。两者合计，我们的工作提供了新的洞察热休克蛋白70旁系同源物的功能特异性使用一个本地客户端蛋白。
The Hsp70 family of molecular chaperones is well-conserved and expressed in all organisms. In budding yeast, cells express four highly similar cytosolic Hsp70s Ssa1, 2, 3 and 4 which arose from gene duplication. Ssa1 and 2 are constitutively expressed while Ssa3 and 4 are induced upon heat shock. Recent evidence suggests that despite their amino acid similarity, these Ssas have unique roles in the cell. Here we examine the relative importance of Ssa1-4 in the regulation of the enzyme ribonucleotide reductase (RNR). We demonstrate that cells expressing either Ssa3 or Ssa4 as their sole Ssa are compromised for their resistance to DNA damaging agents and activation of DNA damage response (DDR)-regulated transcription. In addition, we show that the steady state levels and stability of RNR small subunits Rnr2 and Rnr4 are reduced in Ssa3 or Ssa4-expressing cells, a result of decreased Ssa-RNR interaction. Interaction between the Hsp70 co-chaperone Ydj1 and RNR is correspondingly decreased in cells only expressing Ssa3 and 4. Through studies of Ssa2/4 domain swap chimeras, we determined that the C-terminal domain of Ssas are the source of this functional specificity. Taking together, our work suggests a distinct role for Ssa paralogs in regulating DNA replication mediated by C-terminus sequence variation. Cells require molecular chaperones to fold proteins into their active conformation. A major mystery however is why cells express so many highly-related and apparently redundant Hsp70 paralogs. We examined the role of four Hsp70 paralogs in budding yeast (Ssa1, 2, 3 and 4) on the activity of the ribonucleotide reductase (RNR complex). Importantly, we demonstrate there is selectivity of RNR subunits for Ssa1 and Ssa2 subunits, which is dictated by the co-chaperone Ydj1. Taken together, our work provides new insight into the functional specificity of Hsp70 paralogs using a native client protein.
登录
查看更多内容
影响因子：
4.5
作者：
Gupta A;Puri A;Singh P;Sonam S;Pandey R;Sharma D
通讯作者：
Sharma D
细胞质 Hsp70s 在长寿保证和蛋白质质量控制中的不同作用
影响因子：
4.5
作者：
Andersson R;Eisele-Bürger AM;Hanzén S;Vielfort K;Öling D;Eisele F;Johansson G;Gustafsson T;Kvint K;Nyström T
通讯作者：
Nyström T
表达SSA1，SSA2，SSA3或SSA4的酵母细胞的全局转录本和表型分析是胞质HSP70-SSA伴侣活性的唯一来源。
影响因子：
4.4
作者：
Hasin N;Cusack SA;Ali SS;Fitzpatrick DA;Jones GW
通讯作者：
Jones GW
影响因子：
13.8
作者：
Craig EA;Marszalek J
通讯作者：
Marszalek J
影响因子：
7.7
作者：
Assenza, Salvatore;Sassi, Alberto Stefano;Barducci, Alessandro
通讯作者：
Barducci, Alessandro