Cryo-EM structure of the ancient eukaryotic ribosome from the human parasite Giardia lamblia.

Cryo-EM structure of the ancient eukaryotic ribosome from the human parasite Giardia lamblia.
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DOI:
10.1093/nar/gkac046
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发表时间:
2022-02-22
影响因子:
14.9
通讯作者:
Yonath A
Yonath A
中科院分区:
生物学2区
文献类型:
--
作者:
Hiregange DG;Rivalta A;Bose T;Breiner-Goldstein E;Samiya S;Cimicata G;Kulakova L;Zimmerman E;Bashan A;Herzberg O;Yonath A

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贾第虫病是由原生生物贾第虫引起的一种疾病。由于迄今为止尚未批准针对贾第鞭毛虫病的人类疫苗,而且对现有药物的耐药性正在蔓延,因此需要制定防治贾第鞭毛虫病的新战略。共和党由于其与大多数真核生物和原核生物的核糖体的明显序列差异,Lamblia核糖体可能提供有希望的治疗靶点。在此,我们报道了G. Lamblia(WB株)核糖体在2.75 nm分辨率下测定。核糖体RNA是真核生物中已知的最短的,并且几乎缺乏所有真核生物特异性的核糖体RNA扩展片段。相比之下,核糖体蛋白通常是具有一些物种特异性插入/延伸的真核生物。大多数典型的亚单位间的桥梁保持除了一个失踪的接触网站。独特的结构特征主要位于核糖体的外围。这些可能被利用作为新的化合物,选择性地抑制寄生虫的核糖体活性的设计的靶位点。
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.
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发表时间: 2020-12-02
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