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

新发现的假定人类线粒体肽基脯氨酰顺/反异构酶 Par17 的功能和进化研究

• 批准号: 31783377
• 负责人: Professor Dr. Peter Bayer
• 金额: --
• 依托单位: Abteilung Strukturelle und Medizinische Biochemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2006
• 资助国家: 德国
• 起止时间: 2005-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/31783377?language=en
• 关键词: Functional; evolutionary; studies; newly; discovered

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.

我们最近描述了人类 Parvulin 的一种新亚型，这是一种在后生动物中高度保守的肽基脯氨酰顺/反异构酶。这种被称为 Par17 的细长 Parvulin 相对于众所周知的 Par14 蛋白，包含 N 端 25 个氨基酸的延伸。二级结构预测包 NPS 预测该延伸将采用 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 末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 结合测定、免疫共沉淀和 RNAi 研究来对 Par17 作为新型线粒体蛋白进行功能表征。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，我们希望确定该信号肽在进化过程中何时获得。