Ribosomes are universal molecular machines that translate messenger RNA into proteins. Depending on what the cells needs for protein synthesis, ribosomes exist in various functional states, and when cells face stressful conditions, their ribosomes may enter into an inactive hibernation state. In bacteria, this ability to become dormant through ribosomal hibernation plays a crucial role in their survival, especially when the cells are targeted by ribosome-targeting antibiotics. The phenomenon occurs when ribosomes bind with hibernation factors. In this work, we examine how these special proteins interact with ribosomes from four different Gram-negative pathogens, and how this leads to translation inhibition, reporting the single-particle cryo-electron microscopy structures of hibernating ribosomes from P. aeruginosa, E. hormaechei, K. quasipneumoniae and A. baumannii . We show that these ribosomal complexes contain either short HPF or YfiA tightly bound to the 30S A-site, P-site, and even occasionally to the E-site. Our results provide valuable insights into the ribosomal hibernation mechanism, paving the way to both a better understanding of bacterial dormancy and the possibility of developing antibiotics that target hibernating ribosomes rather than just active ones.
Vasanthakrishnan et al. (Tue,) studied this question.