Abstract
To date, cryo-electron microscopy has become the most successful technique for exploring the structure of the ribosome and for studying binding positions of its various ligands, with the resolution slowly extending toward 10 Å. Obstacles in the attempts to improve resolution are the limited stability and coherence of the electron microscope, the statistics of data collection, and the conformational heterogeneity of the specimen. The last factor in this list proved to be the reason why it has been difficult to go past 18-20 Å with many specimens despite the use of state-of-the-art electron microscopes and inclusion of tens of thousand of projections. A breakthrough has been achieved with a protein synthesis initiation-like complex in which mRNA and fMet-tRNA is bound to the E. coli ribosome. The high occupancy and extraordinary conformational homogeneity of this specimen has enabled us to reach a resolution of 15 Å.