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

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:
; ; ;  [1]
  1. (Yale)
Publication Date:
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.
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.
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.
@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}
}