Research group solves basic problem of molecular biology
Scientists at Charité - Universitätsmedizin Berlin in cooperation with research groups at several German and U.S. research sites, could answer a key question in the production of proteins in the cell. The researchers whose work was published in the leading professional magazine "Nature"* see a possible application of this discovery in the development of improved antibiotics.
Proteins are synthesized with the help of two nucleic acids (RNA) by Ribosomes, the "protein factories" of the cell. Thereby, the so called messenger RNA (mRNA), the blueprint of proteins, can be read much as a magnetic film at the interface between the two subunits of the Ribosome. The proteins are then assembled chain like from amino acids. Readers of the mRNA and at the same time bearers of the amino acids are the so-called transfer-RNAs (tRNAs). These transport amino acids to synthesize the required protein to the site of synthesis, until the blueprint signals the end of this work. Thus, the genetic information stored in the sequence of nucleic acids has been translated from the nucleic acid world into a product of the protein world. The completed protein then leaves through a Ribosome tunnel. At this time, it is not yet clear how the RNA and transfer RNA is moved through the ribosome during this process.
Researchers from Berlin, Marburg, Munich, Frankfurt / Main, Los Alamos, San Diego, Tallahassee and Houston have now managed to document that the motion comes from the opposing rotations of the two subunits of the Ribosome.
“Thereby thermal energy is used; it provides for the internal movement of the Ribosoms, and this in turn moves the tRNAs and mRNA through the ribosome" explained Prof. Christian M.T. Spahn of the Institute for Medical Physics and Biophysics, Campus Charité Mitte, the multinational research group coordinator. The work of the subunits of the Ribosome can be compared with a mechanical ratchet. The head domain of the small subunit assumes a key position, by transporting the tRNAs as on an assembly line. This operation is moderated with the help of a helper protein, which functions as a dynamic pawl to ensure movement in the target direction.
The solution to this long-standing problem in molecular biology was made possible by structural analysis using three-dimensional cryo-electron microscopy.
In this method, the Ribosomes were Quick Frozen in liquid ethane at minus 192 ° Celsius, and several 100,000 two-dimensional images of Ribosomes, were computationally sorted and back-projected into two three-dimensional reconstructions of the ribosome in different structural states.
*Andreas H. Ratje et al.: Head swivel on the ribosome facilitates translocation by means of intra-subunit tRNA hybrid sites. In: Nature, Volume 468, 02 Dezember 2010, 713–716. DOI: 10.1038/nature09547
Prof. Christian Spahn
Institut für Medizinische Physik und Biophysik
Campus Charité Mitte
t: +49 30 450 524131
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