Protein synthesis is a universally conserved process that is assured by a macromolecule called the ribosome (3.4 – 4.5 Mda). In spite of the conservation of the ribosome among all orders of life, its structure presents significant differences between eukaryotes and bacteria. Bacterial ribosome, smaller than its eukaryotic counterpart, presents specific particularities to which we owe the efficiency of numerous commonly used antibiotics that target the latter without hindering protein synthesis in the host. Such structural differences are found in all steps of protein translation.
Here, we attempt to explore by cryo-electron microscopy the ribosomal hibernation, one of the most mysterious regulation processes of protein translation in bacteria. Hibernation is a vital process that can be triggered as a response to stress and aims at shutting down translation in a reversible manner so that translation can recover quickly after the alleviation of stress. Here, we show several 3D reconstructions of hibernation ribosomal complexes from the Gram-positive pathogenic bacteria Staphylococcus aureus. Our structures display the formation of a disome (ribosomal dimer) mediated by a peculiar hibernation factor (HPF), thus setting up the disome in a unique fashion, different than other dimers of known bacterial species indicating the uniqueness of this process in S. aureus and perhaps in gram-positive bacteria more generally. In spite of the size of the imaged asymmetric complexes (~7 Mda, ~550Å diameter), our data-processing yielded several structures after particle sorting presenting an average resolution of ~3.7Å, thus enabling the modelling ab initio of S. aureus HPF, so far of unknown structure.
Our results represent a significant advance and pinpoint a unique process that can be targeted for designing drugs of improved specificity and efficiency against this dangerous pathogen and Gram-positive bacteria more generally.
To cite this abstract:Iskander Khusainov, Quentin Vicens, Anthony Bochler, Alexander Myasinkov, Srefano Marzi, Pascale Romby, Gulnara Yusupova, Marat Yusupov, Yaser Hashem; Structure of hibernating ribosomal complexes from Gram-positive pathogenic bacteria Staphylococcus aureus, solved by single particle cryo-EM. The 16th European Microscopy Congress, Lyon, France. https://emc-proceedings.com/abstract/structure-of-hibernating-ribosomal-complexes-from-gram-positive-pathogenic-bacteria-staphylococcus-aureus-solved-by-single-particle-cryo-em/. Accessed: December 2, 2023
EMC Abstracts - https://emc-proceedings.com/abstract/structure-of-hibernating-ribosomal-complexes-from-gram-positive-pathogenic-bacteria-staphylococcus-aureus-solved-by-single-particle-cryo-em/