Role of the chaperonin cofactor Hsp10 in protein folding and sorting in yeast mitochondria.
Role of the chaperonin cofactor Hsp10 in protein folding and sorting in yeast mitochondria.
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DOI：
10.1083/jcb.126.2.305
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发表时间：
1994-07
期刊：
影响因子：
--
通讯作者：
Hartl FU
中科院分区：
文献类型：
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作者：
Höhfeld J;Hartl FU
线粒体中的蛋白质折叠是由E.ColiGroEL的同源物伴侣蛋白Hsp60介导的。线粒体还含有一种名为Hsp10的辅伴蛋白GROES的同系物，它是伴侣蛋白的功能调节器。为了确定辅伴蛋白在体内的作用，我们使用了酿酒酵母的遗传和生化潜力。对hsp10基因进行了克隆和测序，获得了对温度敏感的致死突变体。我们的结果表明，Hsp10是线粒体蛋白质折叠装置的重要组成部分，参与Hsp60功能的各个方面。HSP10是蛋白质折叠和组装所必需的，它参与了某些蛋白质的分选，如Rieske Fe/S蛋白，在通过基质到达膜间隙的过程中。胞浆二氢叶酸还原酶(DHFR)前体的折叠以融合蛋白的形式输入线粒体，显然不依赖于HSP10的功能，这与伴侣蛋白在体外对DHFR折叠的观察一致。HSP10的温度敏感突变映射到一个结构域(残基25-40)，该结构域对应于先前发现的细菌GROE的移动环区，并导致HSP10在不允许的温度下与伴侣蛋白的结合亲和力降低。
Protein folding in mitochondria is mediated by the chaperonin Hsp60, the homologue of E. coli GroEL. Mitochondria also contain a homologue of the cochaperonin GroES, called Hsp10, which is a functional regulator of the chaperonin. To define the in vivo role of the co- chaperonin, we have used the genetic and biochemical potential of the yeast S. cerevisiae. The HSP10 gene was cloned and sequenced and temperature-sensitive lethal hsp10 mutants were generated. Our results identify Hsp10 as an essential component of the mitochondrial protein folding apparatus, participating in various aspects of Hsp60 function. Hsp10 is required for the folding and assembly of proteins imported into the matrix compartment, and is involved in the sorting of certain proteins, such as the Rieske Fe/S protein, passing through the matrix en route to the intermembrane space. The folding of the precursor of cytosolic dihydrofolate reductase (DHFR), imported into mitochondria as a fusion protein, is apparently independent of Hsp10 function consistent with observations made for the chaperonin-mediated folding of DHFR in vitro. The temperature-sensitive mutations in Hsp10 map to a domain (residues 25-40) that corresponds to a previously identified mobile loop region of bacterial GroES and result in a reduced binding affinity of hsp10 for the chaperonin at the non-permissive temperature.