Structural features within the nascent chain regulate alternative targeting of secretory proteins to mitochondria
Structural features within the nascent chain regulate alternative targeting of secretory proteins to mitochondria
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DOI：
10.1038/emboj.2013.46
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发表时间：
2013-04-03
期刊：
影响因子：
11.4
通讯作者：
Tatzelt, Joerg
中科院分区：
文献类型：
--
作者：
Pfeiffer, Natalie V.;Dirndorfer, Daniela;Tatzelt, Joerg
靶向特定细胞隔间的蛋白质对于维持细胞功能和内环境平衡是必不可少的。在真核细胞中，有两条主要途径依赖于N端信号肽将蛋白质靶向内质网(ER)或线粒体。在这项研究中，我们证明了Pron蛋白样蛋白Shadoo、神经肽激素生长抑素和淀粉样前体蛋白的ER信号肽具有介导线粒体选择性靶向的性质。值得注意的是，这些信号肽的靶向是由新生链内的结构元件决定的。每个识别的信号肽都能有效地促进含有α-螺旋结构域的新生链的内质网输入，但靶向线粒体的非结构多肽。此外，我们观察到内质网信号肽对线粒体的靶向性与内质网导入效率呈负相关。当内质网导入受到影响时，对线粒体的靶向性增强，而提高内质网导入效率则降低线粒体的靶向性。总之，我们的研究揭示了一种新的双重靶向内质网或线粒体的机制，这种机制是由新生链内的结构特征介导的。EMBO期刊(2013)32,1036-1051。DOI：10.1038/Intemj.2013.46；2013年3月12日在线发布
Protein targeting to specified cellular compartments is essential to maintain cell function and homeostasis. In eukaryotic cells, two major pathways rely on N-terminal signal peptides to target proteins to either the endoplasmic reticulum (ER) or mitochondria. In this study, we show that the ER signal peptides of the prion protein-like protein shadoo, the neuropeptide hormone somatostatin and the amyloid precursor protein have the property to mediate alternative targeting to mitochondria. Remarkably, the targeting direction of these signal peptides is determined by structural elements within the nascent chain. Each of the identified signal peptides promotes efficient ER import of nascent chains containing alpha-helical domains, but targets unstructured polypeptides to mitochondria. Moreover, we observed that mitochondrial targeting by the ER signal peptides correlates inversely with ER import efficiency. When ER import is compromised, targeting to mitochondria is enhanced, whereas improving ER import efficiency decreases mitochondrial targeting. In conclusion, our study reveals a novel mechanism of dual targeting to either the ER or mitochondria that is mediated by structural features within the nascent chain. The EMBO Journal (2013) 32, 1036-1051. doi:10.1038/emboj.2013.46; Published online 12 March 2013