Scientists at the Charité – Universitätsmedizin Berlin have discovered a regulatory mechanism that impacts the production of proteins. This mechanism, which exists in higher organisms only, could serve to broaden the scope of antibiotics. The results obtained by the researchers have been published in the current edition of the science journal Cell*.
In evolutionary-biological terms, ribosomes are among the oldest enzymes. Such macromolecular complexes consist of two subunits that can rotate against each other. They are responsible for the production of all proteins in all cells of every organism. In the context of translation ─ i.e. the protein-forming process ─ the genetic code of the protein, so-called messenger RNA (ribonucleic acid), is transcribed at the interface between both subunits of the ribosome. The proteins are then formed from amino acids in a chain-like manner.
Together with other scientists from the Charité's Institute of Medical Physics and Biophysics, Dr. Tatyana Budkevich examined different states of ribosomes on the basis of cryo-electron microscopy. In this method, the ribosomes are rapidly frozen in order to preserve their original properties. On the basis of numerous two-dimensional projection images taken from different directions, it was possible to reconstruct and visualize the three-dimensional structure of the ribosome with the aid of computer-supported image-processing techniques. In this way the scientists were able to identify a new regulatory mechanism that is triggered by a change in ribosomal architecture. Here, both subunits of the ribosome roll against each other in such a way that a cleft is opened precisely at the location where the amino acids bind to the ribosome. This opening simplifies the binding of the amino acids to the ribosome and may help to improve the speed and precision of protein production. However, this mechanism appears to exist solely in nucleated cells, the so-called eukaryotic cells:
According to Dr. Tatyana Budkevich: "Our results demonstrate that despite the similarities existing between bacterial ribosomes and eukaryotes, in the decisive functional steps they differ from one another more significantly than anticipated. Eukaryotic ribosomes apparently possess an additional mode of inter-subunit rotation." Such differences are particularly important in the development of new antibiotics. Only at those points where human ribosomes are found to differ from bacterial ribosomes, is it possible for drug substances to take effect without causing severe adverse reactions in humans. "The identified regulatory mechanism, i.e. the opening between the subunits of the ribosome, could provide the kind of precise differentiation that is required in the production of more selective medications" said Dr. Budkevich.
*Budkevich TV, Giesebrecht J, Behrmann E, Loerke J, Ramrath DJ, MielkeT, Ismer J, HildebrandPW, Tung CS, Nierhaus KH, Sanbonmatsu KY, SpahnCM . Regulation of the mammalian elongation cycle by ribosomal subunit rolling: a eukaryotic-specific conformational change. Cell 2014 Jul 3. Doi: 10.1016/j.cell.2014.04.044.
Links
Institute of Medical Physics and Biophysics
http://biophysik.charite.de/institut/
Contact
Dr. Tatyana Budkevich
Institute of Medical Physics and Biophysics
Charité – Universitätsmedizin Berlin
t: +49 30 450 524 145
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