The Chaperone Network Connected to Human Ribosome-Associated Complex
The Chaperone Network Connected to Human Ribosome-Associated Complex
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DOI：
10.1128/mcb.00986-10
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发表时间：
2011-03-01
影响因子：
5.3
通讯作者：
Rospert, Sabine
中科院分区：
文献类型：
--
作者：
Jaiswal, Himjyot;Conz, Charlotte;Rospert, Sabine
哺乳动物核糖体相关复合物（mRAC）由J结构域蛋白MPP 11和非典型Hsp 70同源物Hsp 70 L1组成，可部分补充来自酿酒酵母的RAC同源复合物的功能。RAC是70-同源物Ssb的唯一J结构域配偶体，其直接且独立于RAC与核糖体结合。我们在这里表明，生长缺陷，由于mRAC耗尽在HeLa细胞类似于那些缺乏RAC的酵母菌株。然而，功能保守性并没有延伸到mRAC的70-同源物伴侣。没有一个主要的人类70-同源物能够补充缺乏SSB的酵母菌株的生长缺陷，或者以类似SSB的方式与核糖体结合。相反，我们的数据表明，mRAC是一个特定的合作伙伴的人热休克蛋白70，但不是其密切的同源Hsc 70。在一个机制水平上，ATP结合，但不是ATP水解，热休克蛋白70 L1影响mRAC的功能作为一个J-结构域伴侣的热休克蛋白70。综合数据表明，虽然功能保守，酵母和哺乳动物细胞已经发展出不同的解决方案，以确保热休克蛋白70型分子伴侣可以有效地协助新合成的多肽链的生物合成。
Mammalian ribosome-associated complex (mRAC), consisting of the J-domain protein MPP11 and the atypical Hsp70 homolog (70-homolog) Hsp70L1, can partly complement the function of RAC, which is the homologous complex from Saccharomyces cerevisiae. RAC is the J-domain partner exclusively of the 70-homolog Ssb, which directly and independently of RAC binds to the ribosome. We here show that growth defects due to mRAC depletion in HeLa cells resemble those of yeast strains lacking RAC. Functional conservation, however, did not extend to the 70-homolog partner of mRAC. None of the major human 70-homologs was able to complement the growth defects of yeast strains lacking Ssb or was bound to ribosomes in an Ssb-like manner. Instead, our data suggest that mRAC was a specific partner of human Hsp70 but not of its close homolog Hsc70. On a mechanistic level, ATP binding, but not ATP hydrolysis, by Hsp70L1 affected mRAC's function as a J-domain partner of Hsp70. The combined data indicate that, while functionally conserved, yeast and mammalian cells have evolved distinct solutions to ensure that Hsp70-type chaperones can efficiently assist the biogenesis of newly synthesized polypeptide chains.