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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Cyclophilin catalyzes protein folding in yeast mitochondria.
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Cyclophilin catalyzes protein folding in yeast mitochondria.

机译:亲环蛋白催化酵母线粒体中的蛋白质折叠。

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摘要

Cyclophilins are a family of ubiquitous proteins that are the intracellular target of the immunosuppressant drug cyclosporin A. Although cyclophilins catalyze peptidylprolyl cis-trans isomerization in vitro, it has remained open whether they also perform this function in vivo. Here we show that Cpr3p, a cyclophilin in the matrix of yeast mitochondria, accelerates the refolding of a fusion protein that was synthesized in a reticulocyte lysate and imported into the matrix of isolated yeast mitochondria. The fusion protein consisted of the matrix-targeting sequence of subunit 9 of F1F0-ATPase fused to mouse dihydrofolate reductase. Refolding of the dihydrofolate reductase moiety in the matrix was monitored by acquisition of resistance to proteinase K. The rate of refolding was reduced by a factor of 2-6 by 2.5 microM cyclosporin A. This reduced rate of folding was also observed with mitochondria lacking Cpr3p. In these mitochondria, protein folding was insensitive to cyclosporin A. The rate of protein import was not affected by cyclosporin A or by deletion of Cpr3p.
机译:亲环蛋白是作为免疫抑制剂药物环孢菌素A的细胞内靶标的泛在蛋白家族。尽管亲环蛋白在体外催化肽基脯氨酰顺反异构化,但是它们是否在体内也执行此功能仍是未知的。在这里,我们显示Cpr3p,一种酵母线粒体基质中的亲环蛋白,可加速网状细胞裂解液中合成并导入分离的酵母线粒体基质中的融合蛋白的重折叠。融合蛋白由与小鼠二氢叶酸还原酶融合的F1F0-ATPase 9亚基的基质靶向序列组成。通过获得对蛋白酶K的抗性来监测基质中二氢叶酸还原酶部分的重折叠。通过2.5 microM环孢菌素A将重折叠的速率降低2-6倍。对于缺乏Cpr3p的线粒体,也观察到这种降低的折叠速率。在这些线粒体中,蛋白质折叠对环孢菌素A不敏感。蛋白质的导入速率不受环孢菌素A或Cpr3p缺失的影响。

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