Abstract

Resolving first crystal structures of prokaryotic and eukaryotic ribosomes by our group has been based on the knowledge accumulated over the decades of studies, starting with the first electron microscopy images of the ribosome obtained by J. Pallade in 1955. In 1983, A. Spirin, then a Director of the Protein Research Institute of the USSR Academy of Sciences, initiated the first study aimed at solving the structure of ribosomes using X-ray structural analysis. In 1999, our group in collaboration with H. Noller published the first crystal structure of entire bacterial ribosome in a complex with its major functional ligands, such as messenger RNA and three transport RNAs at the A, P, and E sites. In 2011, our laboratory published the first atomic-resolution structure of eukaryotic ribosome solved by the X-ray diffraction analysis that confirmed the conserved nature of the main ribosomal functional components, such as the decoding and peptidyl transferase centers, was confirmed, and eukaryote-specific elements of the ribosome were described. Using X-ray structural analysis, we investigated general principles of protein biosynthesis inhibition in eukaryotic ribosomes, along with the mechanisms of antibiotic resistance. Structural differences between bacterial and eukaryotic ribosomes that determine the differences in their inhibition were established. These and subsequent atomic-resolution structures of the functional ribosome demonstrated for the first time the details of binding of messenger and transport RNAs, which was the first step towards understanding how the ribosome structure ultimately determines its functions.

中文翻译：

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原核和真核核糖体原子分辨率结构的途径

摘要

我们小组解析原核和真核核糖体的第一个晶体结构是基于数十年研究积累的知识，从 1955 年 J. Pallade 获得的核糖体的第一张电子显微镜图像开始。1983 年，A. Spirin，时任苏联科学院蛋白质研究所所长，发起了第一项旨在利用 X 射线结构分析解决核糖体结构的研究。1999 年，我们的小组与 H. Noller 合作发表了完整细菌核糖体的第一个晶体结构，与其主要功能配体（如信使 RNA 和 A、P 和 E 位点的三种转运 RNA）形成复合物。在2011年，我们的实验室发表了第一个通过 X 射线衍射分析解决的真核生物核糖体的原子分辨率结构，证实了主要核糖体功能成分（如解码和肽基转移酶中心）的保守性质，并证实了真核生物特异性元素核糖体进行了描述。使用 X 射线结构分析，我们研究了真核生物核糖体中蛋白质生物合成抑制的一般原理，以及抗生素耐药性的机制。确定了细菌和真核核糖体之间的结构差异，这决定了它们抑制的差异。这些和随后的功能性核糖体的原子分辨率结构首次证明了信使和转运 RNA 结合的细节，