How Hibernation Factors RMF, HPF, and YfiA Turn Off Protein Synthesis
The Hibernating Ribosome
When bacteria enter stationary phase, their ribosomes are inactivated. In Escherichia coli, ribosome modulation factor (RMF) causes dimerization of the 70S ribosome and the dimer is stabilized by, hibernation promotion factor (HPF). Alternately, the stationary phase protein, YfiA, inactivates 70S ribosomes. Polikanov et al. (p. 915) present high-resolution structures of the Thermus thermophilus 70S ribosome bound to each of these three factors. The structures suggest that RMF binding inhibits protein synthesis by preventing initial messenger RNA (mRNA) binding and that HPF and YfiA have overlapping binding sites and would both interfere with binding of mRNA, transfer RNA, and initiation factors.
Abstract
Eubacteria inactivate their ribosomes as 100S dimers or 70S monomers upon entry into stationary phase. In Escherichia coli, 100S dimer formation is mediated by ribosome modulation factor (RMF) and hibernation promoting factor (HPF), or alternatively, the YfiA protein inactivates ribosomes as 70S monomers. Here, we present high-resolution crystal structures of the Thermus thermophilus 70S ribosome in complex with each of these stationary-phase factors. The binding site of RMF overlaps with that of the messenger RNA (mRNA) Shine-Dalgarno sequence, which prevents the interaction between the mRNA and the 16S ribosomal RNA. The nearly identical binding sites of HPF and YfiA overlap with those of the mRNA, transfer RNA, and initiation factors, which prevents translation initiation. The binding of RMF and HPF, but not YfiA, to the ribosome induces a conformational change of the 30S head domain that promotes 100S dimer formation.
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References and Notes
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Published In
Science
Volume 336 | Issue 6083
18 May 2012
18 May 2012
Copyright
Copyright © 2012, American Association for the Advancement of Science.
Submission history
Received: 29 December 2011
Accepted: 13 April 2012
Published in print: 18 May 2012
Acknowledgments
We thank the staff at the National Synchrotron Light Source (beamlines X29 and X25) and at the Advanced Photon Source (beamline 24ID) for help during data collection, the staff at the Center for Structural Biology at Yale University for computational support, and S. Seetharaman and M. Gagnon for valuable discussions. This work was supported by NIH grant GM022778 awarded to T.A.S. The structure factors and coordinates for both copies of the 70S ribosome in the asymmetric unit of all complexes have been deposited in the Research Collaboration for Structural Biology Protein Data Bank with the following accession codes: 3V22, 3V23, 3V24, and 3V25 for the RMF-ribosome complex; 3V26, 3V27, 3V28, and 3V29 for the HPF-ribosome complex; and 3V2C, 3V2D, 3V2F, and 3V2E for the YfiA-ribosome complex. T.A.S. owns stock in and is on the advisory board of Rib-X Pharmaceuticals, Inc., which does structure-based drug design targeted at the ribosome.
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- Yury S. Polikanov et al.
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