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首页> 外文期刊>Biochimie >Cis-acting resistance peptides reveal dual ribosome inhibitory action of the macrolide josamycin
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Cis-acting resistance peptides reveal dual ribosome inhibitory action of the macrolide josamycin

机译：顺式作用抗性肽揭示了大环内酯洁沙霉素的双重核糖体抑制作用

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摘要

Macrolide antibiotics block the entrance of nascent peptides to the peptide exit tunnel of the large ribosomal subunit. Expression of specific cis-acting peptides confers low-level macrolide-resistance. We show that, in the case of josamycin, peptide expression does not eject josamycin from the ribosome, implying a peptide resistance mechanism different from that previously suggested for erythromycin. We find dipeptide formation and dipeptidyl-tRNA drop-off in the presence of josamycin to be much slower during translation of resistance than of control mRNAs. We demonstrate low-level josamycin resistance by over-expression of peptidyl-tRNA hydrolase. These findings suggest dual growth-inhibitory action of josamycin by (ⅰ) direct inhibition of peptide-elongation and (ⅱ) indirect inhibition of peptide-elongation through rapid peptidyl-tRNA drop-off, leading to depletion of tRNA isoacceptors available for protein synthesis. We propose that josamycin resistance peptide expression brings ribosomes into a "quarantine" state with small drop-off rate, thereby eliminating the josamycin dependent depletion of tRNA isoacceptors in the protein-synthesis-active state.
机译：大环内酯类抗生素可阻止新生肽进入大核糖体亚基的肽出口通道。特定的顺式作用肽的表达赋予低水平的大环内酯抗性。我们表明，在交霉素的情况下，肽的表达不会从核糖体中排出交霉素，这意味着其肽抗性机制与以前对红霉素所建议的不同。我们发现，在抗性翻译过程中，若沙霉素存在时二肽形成和二肽基-tRNA的下降要比对照mRNA慢得多。我们通过肽基-tRNA水解酶的过表达证明了低水平的沙沙霉素抗性。这些发现表明，通过快速抑制肽基-tRNA的脱落，（osa）直接抑制肽的延伸和（ⅱ）间接抑制肽的延伸，从而产生了柔霉素的双重生长抑制作用，从而导致可用于蛋白质合成的tRNA异构体耗尽。我们提出，若沙霉素抗性肽的表达使核糖体进入“检疫”状态，且脱落率很小，从而消除了在蛋白质合成活性状态下依托沙霉素对tRNA异型受体的消耗。

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  • 来源
    《Biochimie》 |2009年第8期|989-995|共7页
  • 作者

    Martin Lovmar; Vladimir Vimberg; Eliisa Lukk; Karin Nilsson; Tanel Tenson; Mans Ehrenberg;

  • 作者单位

    Department of Cell and Molecular Biology, Uppsala University, BMC, Box 596, SE-75124 Uppsala, Sweden Astra Tech AB, Box 14, SE-43121 Moelndal, Sweden;

    Institute of Technology, Tartu University, 51010 Tartu, Estonia;

    Institute of Technology, Tartu University, 51010 Tartu, Estonia;

    Department of Cell and Molecular Biology, Uppsala University, BMC, Box 596, SE-75124 Uppsala, Sweden;

    Institute of Technology, Tartu University, 51010 Tartu, Estonia;

    Department of Cell and Molecular Biology, Uppsala University, BMC, Box 596, SE-75124 Uppsala, Sweden;

  • 收录信息 美国《科学引文索引》(SCI);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    macrolide; josamycin; protein synthesis; inhibition; resistance;

    机译：大环内酯角霉素蛋白质合成;抑制;抵抗性;

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