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

doi:10.1126/science.1217443

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

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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.

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                    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.  doi:10.1126/science.1217443.

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                    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.  doi:10.1126/science.1217443.

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@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},

  journal      = {Science},

  issn         = {0036-8075},

  number       = 03, 2012,

  volume       = 335,

  place        = {United States},

  year         = {2012},

  month        = {6}

}

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DOI: 10.1126/science.1217443

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