Nature Communications ( IF 14.7 ) Pub Date : 2024-12-17 , DOI: 10.1038/s41467-024-55033-z Chaoyue Wang, Sari Kassem, Rafael Eduardo Oliveira Rocha, Pei Sun, Tan-Trung Nguyen, Joachim Kloehn, Xianyong Liu, Lorenzo Brusini, Alessandro Bonavoglia, Sramona Barua, Fanny Boissier, Mayara Lucia Del Cistia, Hongjuan Peng, Xinming Tang, Fujie Xie, Zixuan Wang, Oscar Vadas, Xun Suo, Yaser Hashem, Dominique Soldati-Favre, Yonggen Jia
The phylum Apicomplexa comprises eukaryotic parasites that cause fatal diseases affecting millions of people and animals worldwide. Their mitochondrial genomes have been significantly reduced, leaving only three protein-coding genes and highly fragmented mitoribosomal rRNAs, raising challenging questions about mitoribosome composition, assembly and structure. Our study reveals how Toxoplasma gondii assembles over 40 mt-rRNA fragments using exclusively nuclear-encoded mitoribosomal proteins and three lineage-specific families of RNA-binding proteins. Among these are four proteins from the Apetala2/Ethylene Response Factor (AP2/ERF) family, originally known as transcription factors in plants and Apicomplexa, now repurposed as essential mitoribosome components. Cryo-EM analysis of the mitoribosome structure demonstrates how these AP2 proteins function as RNA binders to maintain mitoribosome integrity. The mitoribosome is also decorated with members of lineage-specific RNA-binding proteins belonging to RAP (RNA-binding domain abundant in Apicomplexa) proteins and HPR (heptatricopeptide repeat) families, highlighting the unique adaptations of these parasites. Solving the molecular puzzle of apicomplexan mitoribosome could inform the development of therapeutic strategies targeting organellar translation.
中文翻译:
从高度片段化的 rRNA 到功能机器的顶复线粒体核糖体
顶复门由真核寄生虫组成,这些寄生虫会导致影响全球数百万人和动物的致命疾病。它们的线粒体基因组已显著减少,只剩下三个蛋白质编码基因和高度片段化的线粒体 rRNA,这引发了关于线粒体组成、组装和结构的挑战性问题。我们的研究揭示了弓形虫如何使用专门核编码的线粒体蛋白和三个谱系特异性 RNA 结合蛋白家族组装超过 40 个 mt-rRNA 片段。其中包括来自 Apetala2/乙烯反应因子 (AP2/ERF) 家族的四种蛋白质,最初在植物和 Apicomplexa 中被称为转录因子,现在被重新用作必需的核糖体成分。线粒体核糖体结构的冷冻电镜分析展示了这些 AP2 蛋白如何作为 RNA 结合剂发挥作用以维持线粒体核糖体的完整性。线粒体核糖体还装饰有属于 RAP(Apicomplexa 中丰富的 RNA 结合域)蛋白和 HPR(七肽重复序列)家族的谱系特异性 RNA 结合蛋白的成员,突出了这些寄生虫的独特适应。解决顶复复合线粒体核糖体的分子难题可以为开发靶向细胞器翻译的治疗策略提供信息。