Kessler Daniel, Papatheodorou Panagiotis, Stratmann Tina, Dian Elke Andrea, Hartmann-Fatu Cristina, Rassow Joachim, Bayer Peter, Mueller Jonathan Wolf
Department of Structural and Medicinal Biochemistry, Center for Medical Biotechnology - ZMB, University of Duisburg-Essen, 45117 Essen, Germany.
BMC Biol. 2007 Sep 17;5:37. doi: 10.1186/1741-7007-5-37.
The parvulin-type peptidyl prolyl cis/trans isomerase Par14 is highly conserved in all metazoans. The recently identified parvulin Par17 contains an additional N-terminal domain whose occurrence and function was the focus of the present study.
Based on the observation that the human genome encodes Par17, but bovine and rodent genomes do not, Par17 exon sequences from 10 different primate species were cloned and sequenced. Par17 is encoded in the genomes of Hominidae species including humans, but is absent from other mammalian species. In contrast to Par14, endogenous Par17 was found in mitochondrial and membrane fractions of human cell lysates. Fluorescence of EGFP fusions of Par17, but not Par14, co-localized with mitochondrial staining. Par14 and Par17 associated with isolated human, rat and yeast mitochondria at low salt concentrations, but only the Par17 mitochondrial association was resistant to higher salt concentrations. Par17 was imported into mitochondria in a time and membrane potential-dependent manner, where it reached the mitochondrial matrix. Moreover, Par17 was shown to bind to double-stranded DNA under physiological salt conditions.
Taken together, the DNA binding parvulin Par17 is targeted to the mitochondrial matrix by the most recently evolved mitochondrial prepeptide known to date, thus adding a novel protein constituent to the mitochondrial proteome of Hominidae.
微小菌素型肽基脯氨酰顺/反异构酶Par14在所有后生动物中高度保守。最近鉴定出的微小菌素Par17含有一个额外的N端结构域，其出现和功能是本研究的重点。
基于人类基因组编码Par17而牛和啮齿动物基因组不编码这一观察结果，克隆并测序了来自10种不同灵长类物种的Par17外显子序列。Par17在包括人类在内的人科物种基因组中编码，但在其他哺乳动物物种中不存在。与Par14不同，在人细胞裂解物的线粒体和膜部分发现了内源性Par17。Par17（而非Par14）的EGFP融合蛋白的荧光与线粒体染色共定位。Par14和Par17在低盐浓度下与分离的人、大鼠和酵母线粒体相关，但只有Par17与线粒体的结合对更高盐浓度具有抗性。Par17以时间和膜电位依赖的方式导入线粒体，并到达线粒体基质。此外，在生理盐条件下，Par17被证明能与双链DNA结合。
综上所述，DNA结合微小菌素Par17通过迄今已知的最新进化的线粒体前肽靶向线粒体基质，从而为人类线粒体蛋白质组增添了一种新的蛋白质成分。
