Structural basis for the rescue of stalled ribosomes: Structure of YaeJ bound to the ribosome

Matthieu Gagnon, Sai V. Seetharaman, David Bulkley, Thomas A. Steitz

Research output: Contribution to journalArticle

65 Citations (Scopus)

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 tRNAifMet 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.

Original languageEnglish (US)
Pages (from-to)1370-1372
Number of pages3
JournalScience
Volume335
Issue number6074
DOIs
StatePublished - Mar 16 2012
Externally publishedYes

Fingerprint

Ribosomes
Messenger RNA
Transfer RNA
Thermus thermophilus
Gram-Negative Bacteria
Hydrolysis
Bacteria
Proteins

ASJC Scopus subject areas

  • General

Cite this

Structural basis for the rescue of stalled ribosomes : Structure of YaeJ bound to the ribosome. / Gagnon, Matthieu; Seetharaman, Sai V.; Bulkley, David; Steitz, Thomas A.

In: Science, Vol. 335, No. 6074, 16.03.2012, p. 1370-1372.

Research output: Contribution to journalArticle

Gagnon, Matthieu ; Seetharaman, Sai V. ; Bulkley, David ; Steitz, Thomas A. / Structural basis for the rescue of stalled ribosomes : Structure of YaeJ bound to the ribosome. In: Science. 2012 ; Vol. 335, No. 6074. pp. 1370-1372.
@article{090132aed9dd4254abb78dfd4923244a,
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 tRNAifMet 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.",
author = "Matthieu Gagnon and Seetharaman, {Sai V.} and David Bulkley and Steitz, {Thomas A.}",
year = "2012",
month = "3",
day = "16",
doi = "10.1126/science.1217443",
language = "English (US)",
volume = "335",
pages = "1370--1372",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6074",

}

TY - JOUR

T1 - Structural basis for the rescue of stalled ribosomes

T2 - Structure of YaeJ bound to the ribosome

AU - Gagnon, Matthieu

AU - Seetharaman, Sai V.

AU - Bulkley, David

AU - Steitz, Thomas A.

PY - 2012/3/16

Y1 - 2012/3/16

N2 - 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 tRNAifMet 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.

AB - 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 tRNAifMet 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.

UR - http://www.scopus.com/inward/record.url?scp=84858309380&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84858309380&partnerID=8YFLogxK

U2 - 10.1126/science.1217443

DO - 10.1126/science.1217443

M3 - Article

C2 - 22422986

AN - SCOPUS:84858309380

VL - 335

SP - 1370

EP - 1372

JO - Science

JF - Science

SN - 0036-8075

IS - 6074

ER -