Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20742-4454, USA.
Nucleic Acids Res. 2022 Feb 22;50(3):1770-1782. doi: 10.1093/nar/gkac046.
Giardiasis is a disease caused by the protist Giardia lamblia. As no human vaccines have been approved so far against it, and resistance to current drugs is spreading, new strategies for combating giardiasis need to be developed. The G. lamblia ribosome may provide a promising therapeutic target due to its distinct sequence differences from ribosomes of most eukaryotes and prokaryotes. Here, we report the cryo-electron microscopy structure of the G. lamblia (WB strain) ribosome determined at 2.75 Å resolution. The ribosomal RNA is the shortest known among eukaryotes, and lacks nearly all the eukaryote-specific ribosomal RNA expansion segments. In contrast, the ribosomal proteins are typically eukaryotic with some species-specific insertions/extensions. Most typical inter-subunit bridges are maintained except for one missing contact site. Unique structural features are located mainly at the ribosome's periphery. These may be exploited as target sites for the design of new compounds that inhibit selectively the parasite's ribosomal activity.
贾第虫病是由原生动物蓝氏贾第鞭毛虫引起的疾病。由于目前还没有针对该疾病的人类疫苗获得批准，而且对现有药物的耐药性正在蔓延，因此需要开发新的贾第虫病防治策略。由于其核糖体与大多数真核生物和原核生物的核糖体在序列上存在明显差异，因此蓝氏贾第鞭毛虫（WB 株）核糖体可能是一个有前途的治疗靶点。在这里，我们报告了 2.75Å 分辨率下蓝氏贾第鞭毛虫（WB 株）核糖体的冷冻电镜结构。该核糖体 RNA 是已知真核生物中最短的，几乎缺少所有真核生物特有的核糖体 RNA 扩展片段。相比之下，核糖体蛋白通常是真核生物的，具有一些种特异性的插入/延伸。除了一个缺失的接触位点外，大多数典型的亚基间桥都得以保留。独特的结构特征主要位于核糖体的外周。这些特征可能被用作设计新化合物的靶点，这些化合物可以选择性地抑制寄生虫的核糖体活性。
