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Defining the physiological role of SRP in protein-targeting efficiency and specificity

机译:定义SRP在蛋白质靶向效率和特异性中的生理作用

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摘要

The signal recognition particle (SRP) enables cotranslational delivery of proteins for translocation into the endoplasmic reticulum (ER), but its full in vivo role remains incompletely explored. We combined rapid auxin-induced SRP degradation with proximity-specific ribosome profiling to define SRP's in vivo function in yeast. Despite the classic view that SRP recognizes amino-terminal signal sequences, we show that SRP was generally essential for targeting transmembrane domains regardless of their position relative to the amino terminus. By contrast, many proteins containing cleavable amino-terminal signal peptides were efficiently cotranslationally targeted in SRP's absence. We also reveal an unanticipated consequence of SRP loss: Transcripts normally targeted to the ER were mistargeted to mitochondria, leading to mitochondrial defects. These results elucidate SRP's essential roles in maintaining the efficiency and specificity of protein targeting.
机译:信号识别颗粒(SRP)能够将蛋白共翻译传递,以便易位进入内质网(ER),但是其完整的体内作用仍未得到充分研究。我们将生长素诱导的SRP快速降解与邻近特异性核糖体分析相结合,以定义SRP在酵母中的体内功能。尽管经典观点认为SRP可以识别氨基末端信号序列,但我们表明SRP通常对于靶向跨膜结构域至关重要,无论其相对于氨基末端的位置如何。相比之下,在不存在SRP的情况下,许多含有可裂解的氨基末端信号肽的蛋白质都可以有效地共翻译。我们还揭示了SRP丢失的意外后果:通常将靶向ER的转录物误靶向线粒体,导致线粒体缺陷。这些结果阐明了SRP在维持蛋白质靶向效率和特异性方面的重要作用。

著录项

  • 来源
    《Science》 |2018年第6376期|689-692|共4页
  • 作者单位

    Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA;

    Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA;

    Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA;

    Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
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  • 入库时间 2022-08-18 02:51:02

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