克氏锥虫60S核糖体亚基的结构与组装模型
Structure and assembly model for the Trypanosoma cruzi 60S ribosomal subunit.
作者信息
Liu Zheng, Gutierrez-Vargas Cristina, Wei Jia, Grassucci Robert A, Ramesh Madhumitha, Espina Noel, Sun Ming, Tutuncuoglu Beril, Madison-Antenucci Susan, Woolford John L, Tong Liang, Frank Joachim
机构信息
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032.
Department of Biological Sciences, Columbia University, New York, NY 10027.
出版信息
Proc Natl Acad Sci U S A. 2016 Oct 25;113(43):12174-12179. doi: 10.1073/pnas.1614594113. Epub 2016 Oct 10.
Ribosomes of trypanosomatids, a family of protozoan parasites causing debilitating human diseases, possess multiply fragmented rRNAs that together are analogous to 28S rRNA, unusually large rRNA expansion segments, and r-protein variations compared with other eukaryotic ribosomes. To investigate the architecture of the trypanosomatid ribosomes, we determined the 2.5-Å structure of the Trypanosoma cruzi ribosome large subunit by single-particle cryo-EM. Examination of this structure and comparative analysis of the yeast ribosomal assembly pathway allowed us to develop a stepwise assembly model for the eight pieces of the large subunit rRNAs and a number of ancillary "glue" proteins. This model can be applied to the characterization of Trypanosoma brucei and Leishmania spp. ribosomes as well. Together with other details, our atomic-level structure may provide a foundation for structure-based design of antitrypanosome drugs.
锥虫是一类导致人类衰弱性疾病的原生动物寄生虫，其核糖体拥有多个片段化的rRNA，这些rRNA合起来类似于28S rRNA，具有异常大的rRNA扩展片段，并且与其他真核生物核糖体相比存在r蛋白变异。为了研究锥虫核糖体的结构，我们通过单颗粒冷冻电镜确定了克氏锥虫核糖体大亚基的2.5埃结构。对该结构的研究以及对酵母核糖体组装途径的比较分析，使我们能够为大亚基rRNA的八个片段和一些辅助“胶水”蛋白建立一个逐步组装模型。该模型也可应用于布氏锥虫和利什曼原虫核糖体的表征。连同其他细节，我们的原子水平结构可能为基于结构的抗锥虫药物设计提供基础。
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