The chaperones MPP11 and Hsp70L1 form the mammalian ribosome-associated complex
The chaperones MPP11 and Hsp70L1 form the mammalian ribosome-associated complex
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DOI：
10.1073/pnas.0504400102
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发表时间：
2005-07-19
影响因子：
11.1
通讯作者：
Rospert, S
中科院分区：
文献类型：
--
作者：
Otto, H;Conz, C;Rospert, S
可溶性Hsp 70同源物与所有生命界中的新生多肽协同相互作用。此外，真菌拥有一个专门的Hsp 70系统连接到核糖体，在酿酒酵母中由Hsp 70同系物Ssb 1/2 p，Ssz 1 p和Hsp 40同系物zuotin组成。ssz 1 p和zuotin组装成一个独特的异二聚体复合物，称为核糖体相关复合物。到目前为止，在高等真核生物的核糖体上还没有鉴定出这种专门的分子伴侣。然而，在动物和植物中存在一个蛋白家族，其特征在于N-末端zuotin同源结构域融合到C-末端两重复Myb结构域。这个家族的成员，如人MPP 11和小鼠MIDA 1，参与细胞生长的调节。然而，MPP 11/MIDA 1的具体目标仍然难以捉摸。在这里，我们报告说，MPP 11是本地化的细胞质和协会与核糖体。MPP 11的纯化揭示了它与Hsp 70 L1形成稳定的复合物，Hsp 70 L1是Ssz 1 p的远亲同系物。互补实验表明哺乳动物核糖体相关复合物在酵母中是有功能的。我们的结论是，尽管在氨基酸水平上同源性较低，但核糖体相关伴侣与翻译装置的合作在真核细胞中是非常保守的。
Soluble Hsp70 homologs cotranslationally interact with nascent polypeptides in all kingdoms of life. In addition, fungi possess a specialized Hsp70 system attached to ribosomes, which in Saccharomyces cerevisiae consists of the Hsp70 homologs Ssb1/2p, Ssz1p, and the Hsp40 homolog zuotin. Ssz1p and zuotin are assembled into a unique heterodimeric complex termed ribosome-associated complex. So far, no such specialized chaperones have been identified on ribosomes of higher eukaryotes. However, a family of proteins characterized by an N-terminal zuotin-homology domain fused to a C-terminal two-repeat Myb domain is present in animals and plants. Members of this family, like human MPP11 and mouse MIDA1, have been implicated in the regulation of cell growth. Specific targets of MPP11/MIDA1, however, have remained elusive. Here, we report that MPP11 is localized to the cytosol and associates with ribosomes. Purification of MPP11 revealed that it forms a stable complex with Hsp70L1, a distantly related homolog of Ssz1p. Complementation experiments indicate that mammalian ribosome-associated complex is functional in yeast. We conclude that despite a low degree of homology on the amino acid level cooperation of ribosome-associated chaperones with the translational apparatus is well conserved in eukaryotic cells.