• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Molecular Biology >Intramembrane proteolysis of Mgm1 by the mitochondrial rhomboid protease is highly promiscuous regarding the sequence of the cleaved hydrophobic segment.
【24h】

Intramembrane proteolysis of Mgm1 by the mitochondrial rhomboid protease is highly promiscuous regarding the sequence of the cleaved hydrophobic segment.

机译：关于线粒体菱形蛋白酶的Mgm1膜内蛋白水解在切割的疏水片段的序列上是高度混杂的。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Rhomboids are a family of intramembrane serine proteases that are conserved in bacteria, archaea, and eukaryotes. They are required for numerous fundamental cellular functions such as quorum sensing, cell signaling, and mitochondrial dynamics. Mitochondrial rhomboids form an evolutionarily distinct class of rhomboids. It is largely unclear how their activity is controlled and which substrate determinants are responsible for recognition and cleavage. We investigated these requirements for the mitochondrial rhomboid protease Pcp1 and its substrate Mgm1. In contrast to several other rhomboid proteases, Pcp1 does not require helix-breaking amino acids in the cleaved hydrophobic region of Mgm1, termed 'rhomboid cleavage region' (RCR). Even transmembrane segments of inner membrane proteins that are normally not processed by Pcp1 become cleavable when put in place of the authentic RCR of Mgm1. We further show that mutational alterations of a highly negatively charged region located C-terminally to the RCR led to a strong processing defect. Moreover, we show that the determinants required for Mgm1 processing by mitochondrial rhomboid protease are conserved during evolution, as PARL (the human ortholog of Pcp1) showed similar substrate requirements. These results suggest a surprising promiscuity of the mitochondrial rhomboid protease regarding the sequence requirements of the cleaved hydrophobic segment. We propose a working hypothesis on how the mitochondrial rhomboid protease can, despite this promiscuity, achieve a high specificity in recognizing Mgm1. This hypothesis relates to the exceptional biogenesis pathway of Mgm1.
机译：菱形是膜内丝氨酸蛋白酶的家族，在细菌，古细菌和真核生物中是保守的。它们是众多基本细胞功能（例如群体感应，细胞信号传导和线粒体动力学）所必需的。线粒体菱形形成了进化上独特的菱形类。目前还不清楚如何控制其活性以及哪些底物决定因素负责识别和切割。我们调查了线粒体菱形蛋白酶Pcp1及其底物Mgm1的这些要求。与其他几种菱形蛋白酶不同，Pcp1不需要在Mgm1的疏水切割区域（称为“菱形切割区域”（RCR））中破坏螺旋的氨基酸。当取代Mgm1的真实RCR时，即使通常不被Pcp1处理的内膜蛋白的跨膜片段也可以被切割。我们进一步表明，位于RCR的C端的带负电荷的区域的突变改变导致了强烈的加工缺陷。此外，我们显示线粒体菱形蛋白酶Mgm1处理所需的决定因素在进化过程中是保守的，因为PARL（Pcp1的人类直系同源物）显示了相似的底物要求。这些结果表明线粒体菱形蛋白酶的杂乱性令人惊讶，因为所切割的疏水性片段的序列需要。我们提出了一个可行的假设，即尽管存在这种混杂性，线粒体菱形蛋白酶如何能够在识别Mgm1方面达到很高的特异性。该假设与Mgm1的异常生物发生途径有关。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号