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A Path to the Atomic-Resolution Structures of Prokaryotic and Eukaryotic Ribosomes

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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.

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Abbreviations

cryo-EM:

cryogenic electron microscopy

mRNA:

messenger RNA

DC:

decoding site

PTC:

peptidyl transferase center

rRNA:

ribosomal RNA

tRNA:

transport RNA

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Acknowledgments

The authors are grateful to Sultan Agalarov (Institute of Protein Research, Russian Academy of Sciences) and Daniel Wilson (Hamburg University, Germany) for providing Fig. 3.

Funding

This work was supported by the Russian Science Foundation (project no. 20-65-47031).

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Correspondence to Marat Yusupov.

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The authors declare no conflict of interest in financial or any other sphere. This article does not contain description of studies with human participants or animals performed by any of the authors.

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Yusupova, G., Yusupov, M. A Path to the Atomic-Resolution Structures of Prokaryotic and Eukaryotic Ribosomes. Biochemistry Moscow 86, 926–941 (2021). https://doi.org/10.1134/S0006297921080046

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