Structural Basis for the Rescue of Stalled Ribosomes: Structure of YaeJ Bound to the Ribosome

doi:https://doi.org/10.1126/science.1217443

Title: Structural Basis for the Rescue of Stalled Ribosomes: Structure of YaeJ Bound to the Ribosome

Full Record
Other Related Research

Abstract

In bacteria, the hybrid transfer-messenger RNA (tmRNA) rescues ribosomes stalled on defective messenger RNAs (mRNAs). However, certain gram-negative bacteria have evolved proteins that are capable of rescuing stalled ribosomes in a tmRNA-independent manner. Here, we report a 3.2 angstrom-resolution crystal structure of the rescue factor YaeJ bound to the Thermus thermophilus 70S ribosome in complex with the initiator tRNA{sub i}{sup fMet} and a short mRNA. The structure reveals that the C-terminal tail of YaeJ functions as a sensor to discriminate between stalled and actively translating ribosomes by binding in the mRNA entry channel downstream of the A site between the head and shoulder of the 30S subunit. This allows the N-terminal globular domain to sample different conformations, so that its conserved GGQ motif is optimally positioned to catalyze the hydrolysis of peptidyl-tRNA. This structure gives insights into the mechanism of YaeJ function and provides a basis for understanding how it rescues stalled ribosomes.

Authors:

Gagnon, Matthieu G; Seetharaman, Sai V; Bulkley, David; Steitz, Thomas A ^[1]

Yale

Publication Date:: 2012-06-19

Research Org.:: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Org.:: National Institutes of Health (NIH)

OSTI Identifier:: 1039065

Resource Type:: Journal Article

Journal Name:: Science

Additional Journal Information:: Journal Volume: 335; Journal Issue: 03, 2012; Journal ID: ISSN 0036-8075

Country of Publication:: United States

Language:: ENGLISH

Subject:: 59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; BACTERIA; CRYSTAL STRUCTURE; HYDROLYSIS; PROTEINS; RIBOSOMES; RNA; SENSORS

Citation Formats


                    Gagnon, Matthieu G, Seetharaman, Sai V, Bulkley, David, and Steitz, Thomas A. Structural Basis for the Rescue of Stalled Ribosomes: Structure of YaeJ Bound to the Ribosome.  United States: N. p., 2012. 
        Web.  doi:10.1126/science.1217443.

Copy to clipboard


                    Gagnon, Matthieu G, Seetharaman, Sai V, Bulkley, David, & Steitz, Thomas A. Structural Basis for the Rescue of Stalled Ribosomes: Structure of YaeJ Bound to the Ribosome.  United States.  https://doi.org/10.1126/science.1217443

Copy to clipboard


                    Gagnon, Matthieu G, Seetharaman, Sai V, Bulkley, David, and Steitz, Thomas A. Tue .  
        "Structural Basis for the Rescue of Stalled Ribosomes: Structure of YaeJ Bound to the Ribosome".  United States.  https://doi.org/10.1126/science.1217443.

Copy to clipboard


                    
@article{osti_1039065,

  title        = {Structural Basis for the Rescue of Stalled Ribosomes: Structure of YaeJ Bound to the Ribosome},

  author       = {Gagnon, Matthieu G and Seetharaman, Sai V and Bulkley, David and Steitz, Thomas A},

  abstractNote = {In bacteria, the hybrid transfer-messenger RNA (tmRNA) rescues ribosomes stalled on defective messenger RNAs (mRNAs). However, certain gram-negative bacteria have evolved proteins that are capable of rescuing stalled ribosomes in a tmRNA-independent manner. Here, we report a 3.2 angstrom-resolution crystal structure of the rescue factor YaeJ bound to the Thermus thermophilus 70S ribosome in complex with the initiator tRNA{sub i}{sup fMet} and a short mRNA. The structure reveals that the C-terminal tail of YaeJ functions as a sensor to discriminate between stalled and actively translating ribosomes by binding in the mRNA entry channel downstream of the A site between the head and shoulder of the 30S subunit. This allows the N-terminal globular domain to sample different conformations, so that its conserved GGQ motif is optimally positioned to catalyze the hydrolysis of peptidyl-tRNA. This structure gives insights into the mechanism of YaeJ function and provides a basis for understanding how it rescues stalled ribosomes.},

  doi          = {10.1126/science.1217443},

  url          = {https://www.osti.gov/biblio/1039065},
  journal      = {Science},

  issn         = {0036-8075},

  number       = 03, 2012,

  volume       = 335,

  place        = {United States},

  year         = {2012},

  month        = {6}

}

Copy to clipboard

Journal Article:

https://doi.org/10.1126/science.1217443

Other availability

Find in Google Scholar

Search WorldCat to find libraries that may hold this journal

Save / Share:

Export Metadata

Save to My Library

Similar records in OSTI.GOV collections:

Structural Basis for Translation Termination on the 70S Ribosome

Journal Article Laurberg, M ; Asahara, H ; Korostelev, A ; ... - Nature 454:852,2008

At termination of protein synthesis, type I release factors promote hydrolysis of the peptidyl-transfer RNA linkage in response to recognition of a stop codon. Here we describe the crystal structure of the Thermus thermophilus 70S ribosome in complex with the release factor RF1, tRNA and a messenger RNA containing a UAA stop codon, at 3.2 {angstrom} resolution. The stop codon is recognized in a pocket formed by conserved elements of RF1, including its PxT recognition motif, and 16S ribosomal RNA. The codon and the 30S subunit A site undergo an induced fit that results in stabilization of a conformation ofmore »« less
Formation of the First Peptide Bond: The Structure of EF-P Bound to the 70S Ribosome

Journal Article Blaha, Gregor ; Stanley, Robin E ; Steitz, Thomas A ; ... - Science

Elongation factor P (EF-P) is an essential protein that stimulates the formation of the first peptide bond in protein synthesis. Here we report the crystal structure of EF-P bound to the Thermus thermophilus 70S ribosome along with the initiator transfer RNA N-formyl-methionyl-tRNAi (fMet-tRNA{sub i}{sup fMet}) and a short piece of messenger RNA (mRNA) at a resolution of 3.5 angstroms. EF-P binds to a site located between the binding site for the peptidyl tRNA (P site) and the exiting tRNA (E site). It spans both ribosomal subunits with its amino-terminal domain positioned adjacent to the aminoacyl acceptor stem and its carboxyl-terminalmore »« less
https://doi.org/10.1126/science.1175800
Formation of the First Peptid Bond: the Structure of EF-P Bound to the 70S Ribosome

Journal Article Blaha, G ; Stanley, R ; Steitz, T - Science

Elongation factor P (EF-P) is an essential protein that stimulates the formation of the first peptide bond in protein synthesis. Here we report the crystal structure of EF-P bound to the Thermus thermophilus 70S ribosome along with the initiator transfer RNA N-formyl-methionyl-tRNAi (fMet-tRNAifMet) and a short piece of messenger RNA (mRNA) at a resolution of 3.5 angstroms. EF-P binds to a site located between the binding site for the peptidyl tRNA (P site) and the exiting tRNA (E site). It spans both ribosomal subunits with its amino-terminal domain positioned adjacent to the aminoacyl acceptor stem and its carboxyl-terminal domain positionedmore »« less
https://doi.org/10.1126/science.1175800
Crystal Structure of a Translation Termination Complex Formed With Release Factor RF2

Journal Article Korostelev, A ; Asahara, H ; Lancaster, L ; ... - Proc. Nat. Acad. Sci. 105:19684,2008

We report the crystal structure of a translation termination complex formed by the Thermus thermophilus 70S ribosome bound with release factor RF2, in response to a UAA stop codon, solved at 3 {angstrom} resolution. The backbone of helix -5 and the side chain of serine of the conserved SPF motif of RF2 recognize U1 and A2 of the stop codon, respectively. A3 is unstacked from the first 2 bases, contacting Thr-216 and Val-203 of RF2 and stacking on G530 of 16S rRNA. The structure of the RF2 complex supports our previous proposal that conformational changes in the ribosome in responsemore »« less
Sarecycline interferes with tRNA accommodation and tethers mRNA to the 70S ribosome

Journal Article Batool, Zahra ; Lomakin, Ivan B. ; Polikanov, Yury S. ; ... - Proceedings of the National Academy of Sciences of the United States of America

Sarecycline is a new narrow-spectrum tetracycline-class antibiotic approved for the treatment of acne vulgaris. Tetracyclines share a common four-ring naphthacene core and inhibit protein synthesis by interacting with the 70S bacterial ribosome. Sarecycline is distinguished chemically from other tetracyclines because it has a 7-[[methoxy(methyl)amino]methyl] group attached at the C7 position of ring D. To investigate the functional role of this C7 moiety, we determined the X-ray crystal structure of sarecycline bound to the Thermus thermophilus 70S ribosome. Our 2.8-Å resolution structure revealed that sarecycline binds at the canonical tetracycline binding site located in the decoding center of the small ribosomalmore »« less
https://doi.org/10.1073/pnas.2008671117

Full Text Available

Similar Records