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.

我们最近描述了一种新的亚型的人Parvulin，肽脯氨酰顺/反异构酶，是高度保守的后生动物之间的有机体。相对于公知的Par 14蛋白，这种被称为Par 17的伸长的Parvulin含有N-末端25个氨基酸的延伸。通过二级结构预测软件包ESTA预测该延伸采用α-螺旋构象。它也被细胞定位预测程序认为是推定的线粒体靶向肽。我们计划通过体外摄取实验以及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。这种新的Par 17可以令人满意地解释有争议的讨论定位实验的Parvulin蛋白，发现在细胞核，胞质溶胶和线粒体。此外，我们希望通过DNA结合试验、免疫共沉淀和RNAi研究来表征Par 17作为新的线粒体蛋白的功能。由于Par 17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，我们想确定这种信号肽是在进化过程中获得的。