SecM-stalled ribosomes adopt an altered geometry at the peptidyl transferase center.
As nascent polypeptide chains are synthesized, they pass through a tunnel in the large ribosomal subunit. Interaction between specific nascent chains and the ribosomal tunnel is used to induce translational stalling for the regulation of gene expression. One well-characterized example is the Escheri...
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doaj-7da6875e5218435da7769ad4cdeb42282021-07-02T05:26:24ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852011-01-0191e100058110.1371/journal.pbio.1000581SecM-stalled ribosomes adopt an altered geometry at the peptidyl transferase center.Shashi BhushanThomas HoffmannBirgit SeideltJens FrauenfeldThorsten MielkeOtto BerninghausenDaniel N WilsonRoland BeckmannAs nascent polypeptide chains are synthesized, they pass through a tunnel in the large ribosomal subunit. Interaction between specific nascent chains and the ribosomal tunnel is used to induce translational stalling for the regulation of gene expression. One well-characterized example is the Escherichia coli SecM (secretion monitor) gene product, which induces stalling to up-regulate translation initiation of the downstream secA gene, which is needed for protein export. Although many of the key components of SecM and the ribosomal tunnel have been identified, understanding of the mechanism by which the peptidyl transferase center of the ribosome is inactivated has been lacking. Here we present a cryo-electron microscopy reconstruction of a SecM-stalled ribosome nascent chain complex at 5.6 Å. While no cascade of rRNA conformational changes is evident, this structure reveals the direct interaction between critical residues of SecM and the ribosomal tunnel. Moreover, a shift in the position of the tRNA-nascent peptide linkage of the SecM-tRNA provides a rationale for peptidyl transferase center silencing, conditional on the simultaneous presence of a Pro-tRNA(Pro) in the ribosomal A-site. These results suggest a distinct allosteric mechanism of regulating translational elongation by the SecM stalling peptide.http://europepmc.org/articles/PMC3022528?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shashi Bhushan Thomas Hoffmann Birgit Seidelt Jens Frauenfeld Thorsten Mielke Otto Berninghausen Daniel N Wilson Roland Beckmann |
spellingShingle |
Shashi Bhushan Thomas Hoffmann Birgit Seidelt Jens Frauenfeld Thorsten Mielke Otto Berninghausen Daniel N Wilson Roland Beckmann SecM-stalled ribosomes adopt an altered geometry at the peptidyl transferase center. PLoS Biology |
author_facet |
Shashi Bhushan Thomas Hoffmann Birgit Seidelt Jens Frauenfeld Thorsten Mielke Otto Berninghausen Daniel N Wilson Roland Beckmann |
author_sort |
Shashi Bhushan |
title |
SecM-stalled ribosomes adopt an altered geometry at the peptidyl transferase center. |
title_short |
SecM-stalled ribosomes adopt an altered geometry at the peptidyl transferase center. |
title_full |
SecM-stalled ribosomes adopt an altered geometry at the peptidyl transferase center. |
title_fullStr |
SecM-stalled ribosomes adopt an altered geometry at the peptidyl transferase center. |
title_full_unstemmed |
SecM-stalled ribosomes adopt an altered geometry at the peptidyl transferase center. |
title_sort |
secm-stalled ribosomes adopt an altered geometry at the peptidyl transferase center. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Biology |
issn |
1544-9173 1545-7885 |
publishDate |
2011-01-01 |
description |
As nascent polypeptide chains are synthesized, they pass through a tunnel in the large ribosomal subunit. Interaction between specific nascent chains and the ribosomal tunnel is used to induce translational stalling for the regulation of gene expression. One well-characterized example is the Escherichia coli SecM (secretion monitor) gene product, which induces stalling to up-regulate translation initiation of the downstream secA gene, which is needed for protein export. Although many of the key components of SecM and the ribosomal tunnel have been identified, understanding of the mechanism by which the peptidyl transferase center of the ribosome is inactivated has been lacking. Here we present a cryo-electron microscopy reconstruction of a SecM-stalled ribosome nascent chain complex at 5.6 Å. While no cascade of rRNA conformational changes is evident, this structure reveals the direct interaction between critical residues of SecM and the ribosomal tunnel. Moreover, a shift in the position of the tRNA-nascent peptide linkage of the SecM-tRNA provides a rationale for peptidyl transferase center silencing, conditional on the simultaneous presence of a Pro-tRNA(Pro) in the ribosomal A-site. These results suggest a distinct allosteric mechanism of regulating translational elongation by the SecM stalling peptide. |
url |
http://europepmc.org/articles/PMC3022528?pdf=render |
work_keys_str_mv |
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