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

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.

Automated summary

The first crystal structures of prokaryotic and eukaryotic ribosomes were resolved by the research group based on decades of accumulated knowledge, revealing the conserved nature of ribosomal structure and specific elements in eukaryotes. Through X-ray structural analysis, the group investigated the principles of protein biosynthesis inhibition and antibiotic resistance mechanisms in eukaryotic ribosomes, as well as established the structural differences between bacterial and eukaryotic ribosomes that determine their inhibition. These atomic-resolution structures provided detailed insights into the binding of messenger and transport RNAs, shedding light on how the ribosome structure determines its functions.