Functional and evolutionary studies of the newly discovered putatively mitochondrial human peptidyl-prolyl cis/trans-isomerase Par17

我们最近描述了一种新的人类Parvulin异构体，一种在后生动物中高度保守的肽基脯氨酸顺式/反式异构酶。这种细长的Parvulin称为Par17，与众所周知的Par14蛋白相比，它含有一个n端25个氨基酸的延伸。二级结构预测包NPS预测该扩展将采用α -螺旋构象。它也被细胞定位预测程序认为是假定的线粒体靶向肽。我们计划通过体外摄取实验和体内定位研究来研究这种n端延伸作为线粒体靶向信号。这种新颖的Par17可以令人满意地解释在细胞核、细胞质和线粒体中发现的Parvulin蛋白的有争议的定位实验。此外，我们希望通过DNA结合试验、共免疫沉淀和RNAi研究，在功能上表征Par17作为一种新的线粒体蛋白。由于Par17由人类基因组编码，但在啮齿动物、牛和非哺乳动物基因组中不存在，我们想要确定这种信号肽是在进化过程中何时获得的。

We have recently described a novel isoform of human Parvulin, a peptidyl prolyl cis/trans isomerase that is highly conserved among metazoan organisms. This elongated Parvulin called Par17 contains an N-terminal 25 amino acid extension relative to the well known Par14 protein. This extension is predicted to adopt an alpha-helical conformation by the secondary structure prediction package NPS. It is also recognized as putative mitochondrial targeting peptide by cellular localization prediction programs. We plan to investigate this N-terminal extension as mitochondrial targeting signal by in vitro uptake experiments as well as in vivo localization studies. This novel Par17 could satisfyingly explain controversially discussed localizations experiments of Parvulin proteins that were found in nuclei, cytosol and mitochondria. In addition, we want to functionally characterize Par17 as novel mitochondrial protein by DNA binding assays, co-immunoprecipitations and RNAi studies. As Par17 is encoded by the human genome, but is absent from rodent, bovine and non-mammalian genomes we want to determine when this signal peptide was acquired during evolution.