Laboratory of Protein and Nucleic Acid Chemistry, The Rockefeller University, New York, NY, USA.
Department of Molecular Biology, The Laboratory for Molecular Infection Medicine Sweden, Umeå Centre for Microbial Research, Science for Life Laboratory, Umeå University, Umeå, Sweden.
Nat Microbiol. 2019 Nov;4(11):1798-1804. doi: 10.1038/s41564-019-0514-6. Epub 2019 Jul 22.
Microsporidia are eukaryotic parasites that infect essentially all animal species, including many of agricultural importance, and are significant opportunistic parasites of humans. They are characterized by having a specialized infection apparatus, an obligate intracellular lifestyle, rudimentary mitochondria and the smallest known eukaryotic genomes. Extreme genome compaction led to minimal gene sizes affecting even conserved ancient complexes such as the ribosome. 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 protein-coding genes, provides a mechanism for ribosome inhibition and can serve as a structural basis for the development of inhibitors against microsporidian parasites.
微孢子虫是感染包括许多农业重要物种在内的所有动物物种的真核寄生虫，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装置、严格的细胞内生活方式、基本的线粒体和已知最小的真核基因组。极端的基因组压缩导致最小的基因大小，甚至影响到核糖体等保守的古老复合物。在本研究中，展示了来自微孢子虫 Vairimorpha necatrix 的核糖体的冷冻电子显微镜结构，该结构说明了基因组压缩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丢失和基本上所有真核生物特异性核糖体 RNA(rRNA)扩展片段的去除，从而将 rRNA 减少到功能保守的核心。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。通过两个以前未被表征的休眠因子，微孢子虫核糖体保持在非活性状态，这两个因子特异性靶向功能重要的 E 位、P 位和多肽出口隧道。本研究说明了进化压力对 RNA 和蛋白质编码基因的不同影响，为核糖体抑制提供了一种机制，并可以作为针对微孢子虫寄生虫的抑制剂的开发的结构基础。
