department of pharmacology

Taylor Laboratory

Eukaryotic Ribosome: Structure, Assembly, and Biogenesis


Ribosome

Despite the emergence of a large number of X-ray crystallographic models of the bacterial 70S ribosome over the past decade, an accurate atomic model of the eukaryotic 80S ribosome is still not available. Eukaryotic ribosomes possess more ribosomal proteins and ribosomal RNA than bacterial ribosomes, and are implicated in having several extra-ribosomal functions in the eukaryotic cells. By combining cryo-EM with RNA and protein homology modeling, we have recently constructed an atomic model of the yeast 80S ribosome complete with all ribosomal RNA expansion segments and all ribosomal proteins for which a structural homolog has been identified. Mutation or deletion of 80S ribosomal proteins can abrogate maturation of the ribosome, leading to several human diseases. In addition, biogenesis of eukaryotic ribosomes requires the assistance of hundreds of co-factors. By comparison, bacterial ribosomes assemble under the surveillance of only 20 co-factors or so. Similarly, initiation of protein synthesis requires more than thirteen factors in eukaryotes compared to only three in bacteria. A better understanding of the more advanced processes in eukaryotic ribosome assembly, maturation and biogenesis at a molecular level could lead to the discovery of novel therapeutics aimed at correcting abrogated function.