Ribosomes, the construction sites for proteins, are far more complex than previously assumed. During the production of proteins they constantly and spontaneously change their form. This performance of eukaryotic ribosomes has now been demonstrated for the first time by scientists at Charité - Universitätsmedizin Berlin, the Max-Planck-Institut für Molekulare Genetik in Berlin, and Cornell University in New York, with the aid of special electron microscopic and biophysical methods. The results published in the current issue of the journal "Molecular Cell" are the prerequisite for improving our understanding of the inner workings of the ribosome and its specific interactions with antibiotics.
As cellular factories, ribosomes are responsible for producing proteins so they determine the function and structure of all living cells. They consist of large and small subunits. . During the protein synthesis, the blueprint of a protein, i.e. the so-called messenger RNA (ribonucleic acid), is read like a magnetic film at the interface between the two subunits of the ribosome. According to this genetic information proteins are built as a chain of amino acids. The transfer RNAs are readers of the messenger RNA and at the same time carriers of the amino acids. They transport the specific amino acids required to build the proteins to the site of synthesis until the blueprint indicates that the work has been completed. As a result, the genetic code that is stored in the sequence of nucleic acids has been translated from the nucleic acid world to a product of the protein world. The mode of action of ribosomes from bacteria (organisms without a cell nucleus) is already very well understood. Far less is known about ribosomes from eukaryotes (all organisms with a cell nucleus), and consequently also about human ribosomes. However, eukaryotic ribosomes are much larger and much more complex.
The scientists led by Prof. Christian Spahn, Director of the Institut für Medizinische Physik und Biophysik at Campus Charité Mitte, were now able to show that both L-shaped transfer RNA and ribosomes spontaneously oscillate between different states during the translation process. "For us it was surprising to discover that during bacterial protein biosynthesis and that of the eukaryotes different conformations of the complex between ribosomes and transfer RNA are favored. This indicates divergent strategies in the regulation of protein production and can explain the differing modes of action of antibiotics in different kingdoms of life," says Tatyana Budkevich, the first author of the study, commenting on her results.