Potassium at the heart of protein synthesis
Essential for the vital functions of our body, protein synthesis takes place in our cells at the heart of ribosomes. Researchers from Gulnara Yusupova's team at the IGBMC (CNRS/Inserm/Unistra), in collaboration with Diamond Light Source in the United Kingdom, have identified potassium ions within the functional centres of bacterial ribosomes, a location previously attributed to magnesium ions. Published in Nature communication on March xx, these unexpected results provide a better understanding of the complexity of the structure and function of these large macromolecular complexes.
Genuine molecular machines, ribosomes decipher the information contained in a copy of DNA, called messenger RNA, to synthesize proteins. They "read" the messenger RNA triplets (mRNAs) from the transcription and select the appropriate transfer RNAs (tRNAs). These tRNAs carry amino acids which, when put together, constitute a protein. Ribosomes are thus able to "choose" the right tRNAs that correspond to mRNAs. Composed of proteins and ribosomal RNAs (rRNAs), these large complexes require metal ions to maintain their configuration in space but also to carry out protein synthesis. A role hitherto wrongly attributed to magnesium. Indeed, in the determination of high-resolution structure, the identity of a positive ion specifically linked to an RNA can be very ambiguous: is this drop of density a water molecule? A magnesium? Or anything else? Often a magnesium is placed by default. In recent years, it has become evident that many structures contain poorly assigned ions. This is the case for ribosomal structures.
In this study, thanks to long-wavelength X-ray diffraction, in collaboration with Diamond Light Source, and crystallography, Gulnara Yusupova's team, and in particular Alexis Rosov, also employed at Ribostruct*, were able to describe with unprecedented precision the complexity of the bacterial ribosome structure. They identified hundreds of potassium ions involved in the formation of the three-dimensional structure of rRNA, interactions between rRNA proteins and ribosomal protein structures. They also observed the presence of potassium ions in the functional centres of the ribosome, thus demonstrating their involvement in protein synthesis.
This data expands the fundamental knowledge of ribosome function and structure. This will benefit a large community of scientists interested in various aspects of protein synthesis, from the fundamental principles of ribosome action to pharmaceutical chemistry applications.
This study was funded by the ANR, the Foundation for Medical Research, the Russian government and the Federal University of Kazan.
* The teams of Gulnara Yusupova and Marat Yusupov have constantly improved their techniques and have acquired an undeniable know-how for the crystallization of the eukaryotic ribosome and the study of its functioning. Today, the resolution with which they are able to observe this structure is sufficiently precise for the development of new drugs targeting the eukaryotic ribosome. In 2015, they set up a start-up project, Ribostruct, led by Jean-Paul Renaud, to promote this know-how.