SecM-stalled Ribosomes Adopt an Altered Geometry at the Peptidyl Transferase Center

Overview

Journal PLoS Biol

Specialty Biology

Date 2011 Jan 27

PMID 21267063

Citations 85

Authors

Shashi Bhushan

Thomas Hoffmann

Birgit Seidelt

Jens Frauenfeld

Thorsten Mielke

Otto Berninghausen

Daniel N Wilson

Roland Beckmann

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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The SecM arrest peptide traps a pre-peptide bond formation state of the ribosome.

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RAPP-containing arrest peptides induce translational stalling by short circuiting the ribosomal peptidyltransferase activity.

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