Abstract

Enterococcus faecalis is a gram-positive organism responsible for serious infections in humans, but as with many bacterial pathogens, resistance has rendered a number of commonly used antibiotics ineffective. Here, we report the cryo-EM structure of the E. faecalis 70S ribosome to a global resolution of 2.8 Å. Structural differences are clustered in peripheral and solvent exposed regions when compared with Escherichia coli, whereas functional centres, including antibiotic binding sites, are similar to other bacterial ribosomes. Comparison of intersubunit conformations among five classes obtained after three-dimensional classification identifies several rotated states. Large ribosomal subunit protein bL31, which forms intersubunit bridges to the small ribosomal subunit, assumes different conformations in the five classes, revealing how contacts to the small subunit are maintained throughout intersubunit rotation. A tRNA observed in one of the five classes is positioned in a chimeric pe/E position in a rotated ribosomal state. The 70S ribosome structure of E. faecalis now extends our knowledge of bacterial ribosome structures and may serve as a basis for the development of novel antibiotic compounds effective against this pathogen.

Highlights

  • Enterococcus faecalis is a gram-positive organism responsible for serious infections in humans, but as with many bacterial pathogens, resistance has rendered a number of commonly used antibiotics ineffective

  • In the analysis of the E. faecalis 70S ribosome structure determined by cryo-electron microscopy to a global resolution of 2.8 Å, we find that structural differences are located predominantly in peripheral regions, while the organization of the functional centres and antibiotic binding sites remains conserved

  • The cryo-electron microscopy (cryo-EM) structure of E. faecalis 70S ribosome presented here revealed that the architecture of functional centres and subunit interfaces remain conserved when compared with E. coli and S. aureus

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Summary

Introduction

Enterococcus faecalis is a gram-positive organism responsible for serious infections in humans, but as with many bacterial pathogens, resistance has rendered a number of commonly used antibiotics ineffective. It is quite possible that visualizing ribosomes from a phylogenetically broader range of organisms will reveal structural or functional aspects of the protein synthetic apparatus not seen with the most frequently employed model ­systems[7] This raises the possibility of leveraging such differences to develop more effective and specific antimicrobial therapies. In the analysis of the E. faecalis 70S ribosome structure determined by cryo-electron microscopy (cryo-EM) to a global resolution of 2.8 Å, we find that structural differences are located predominantly in peripheral regions, while the organization of the functional centres and antibiotic binding sites remains conserved. Comparison of intersubunit rotations in five EM classes obtained after three-dimensional classification reveals conformational changes in ribosomal protein bL31 and the presence of a tRNA molecule in a pe/E-like conformation

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