Structure of a hibernating 100S ribosome reveals an inactive conformation of the ribosomal protein S1

Nat Microbiol. 2018 Oct;3(10):1115-1121. doi: 10.1038/s41564-018-0237-0. Epub 2018 Sep 3.


To survive under conditions of stress, such as nutrient deprivation, bacterial 70S ribosomes dimerize to form hibernating 100S particles1. In γ-proteobacteria, such as Escherichia coli, 100S formation requires the ribosome modulation factor (RMF) and the hibernation promoting factor (HPF)2-4. Here we present single-particle cryo-electron microscopy structures of hibernating 70S and 100S particles isolated from stationary-phase E. coli cells at 3.0 Å and 7.9 Å resolution, respectively. The structures reveal the binding sites for HPF and RMF as well as the unexpected presence of deacylated E-site transfer RNA and ribosomal protein bS1. HPF interacts with the anticodon-stem-loop of the E-tRNA and occludes the binding site for the messenger RNA as well as A- and P-site tRNAs. RMF facilitates stabilization of a compact conformation of bS1, which together sequester the anti-Shine-Dalgarno sequence of the 16S ribosomal RNA (rRNA), thereby inhibiting translation initiation. At the dimerization interface, the C-terminus of uS2 probes the mRNA entrance channel of the symmetry-related particle, thus suggesting that dimerization inactivates ribosomes by blocking the binding of mRNA within the channel. The back-to-back E. coli 100S arrangement is distinct from 100S particles observed previously in Gram-positive bacteria5-8, and reveals a unique role for bS1 in translation regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cryoelectron Microscopy
  • Dimerization
  • Escherichia coli / chemistry*
  • Escherichia coli / ultrastructure
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / metabolism*
  • Gene Expression Regulation, Bacterial
  • Models, Molecular*
  • Peptide Chain Initiation, Translational
  • Protein Binding
  • Protein Conformation
  • RNA, Bacterial / metabolism
  • Ribosomal Proteins / chemistry*
  • Ribosomal Proteins / metabolism*
  • Ribosomes / chemistry*
  • Ribosomes / metabolism
  • Ribosomes / ultrastructure


  • Escherichia coli Proteins
  • RNA, Bacterial
  • Ribosomal Proteins
  • ribosomal protein S1, E coli