Evolutionary compaction and adaptation visualized by the structure of the dormant microsporidian ribosome
Evolutionary compaction and adaptation visualized by the structure of the dormant microsporidian ribosome
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DOI：
10.1038/s41564-019-0514-6
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发表时间：
2019-11-01
影响因子：
28.3
通讯作者：
Klinge, Sebastian
中科院分区：
文献类型：
--
作者：
Barandun, Jonas;Hunziker, Mirjam;Klinge, Sebastian
微孢子虫是一种真核寄生虫，基本上可以感染所有动物物种，包括许多重要的农业动物（1-3），也是人类重要的机会性寄生虫。它们的特点是具有专门的感染器官，特定的细胞内生活方式(5)，基本的线粒体和已知最小的真核基因组（5-7）。极端的基因组压缩导致最小的基因大小甚至影响到保守的古老复合物，如核糖体（8-10）。在本研究中，提出了从微孢子虫核基质核糖体的低温电镜结构，这说明了基因组压实是如何导致已知最小的真核细胞质核糖体。选择压力导致两个核糖体蛋白的缺失和几乎所有真核细胞特异性核糖体RNA （rRNA）扩增片段的移除，将rRNA减少到一个功能保守的核心。该结构突出了一种微孢子虫特异性和几种重新利用的现有核糖体蛋白如何补偿广泛的rRNA减少。微孢子虫核糖体被两个先前未被发现的休眠因子保持在非活性状态，这两个休眠因子专门针对功能重要的e位点、p位点和多肽出口通道。本研究阐明了进化压力对RNA和蛋白质编码基因的不同影响，提供了核糖体抑制的机制，并可作为开发抗微孢子虫寄生虫抑制剂的结构基础。
Microsporidia are eukaryotic parasites that infect essentially all animal species, including many of agricultural importance(1-3), and are significant opportunistic parasites of humane. They are characterized by having a specialized infection apparatus, an obligate intracellular lifestyles(5), rudimentary mitochondria and the smallest known eukaryotic genomess(5-7). Extreme genome compaction led to minimal gene sizes affecting even conserved ancient complexes such as the ribosomes(8-10). In the present study, the cryo-electron microscopy structure of the ribosome from the microsporidium Vairimorpha necatrix is presented, which illustrates how genome compaction has resulted in the smallest known eukaryotic cytoplasmic ribosome. Selection pressure led to the loss of two ribosomal proteins and removal of essentially all eukaryote-specific ribosomal RNA (rRNA) expansion segments, reducing the rRNA to a functionally conserved core. The structure highlights how one microsporidia-specific and several repurposed existing ribosomal proteins compensate for the extensive rRNA reduction. The microsporidian ribosome is kept in an inactive state by two previously uncharacterized dormancy factors that specifically target the functionally important E-site, P-site and polypeptide exit tunnel. The present study illustrates the distinct effects of evolutionary pressure on RNA and proteincoding genes, provides a mechanism for ribosome inhibition and can serve as a structural basis for the development of inhibitors against microsporidian parasites.