TCB Publications - Abstract

James Gumbart, Eduard Schreiner, Daniel N. Wilson, Roland Beckmann, and Klaus Schulten. Mechanisms of SecM-mediated stalling in the ribosome. Biophysical Journal, 103:331-341, 2012. (PMC: 3400775)

GUMB2012 Nascent-peptide modulation of translation is a common regulatory mechanism of gene expression. In this mechanism, while still in the exit tunnel of the ribosome, the nascent peptide induces translational pausing, thereby controlling the expression of downstream genes. One example is SecM, which inhibits peptide-bond formation in the ribosome’s peptidyl transferase center (PTC) during its own translation, up-regulating the expression of the protein translocase SecA. While biochemical experiments and cryo-electron microscopy data have led to the identification of some residues involved in SecM recognition, the full pathway of interacting residues connecting SecM to the PTC through the ribosome has not yet been conclusively established. Now, using the cryo-electron microscopy data an atomic model of the SecM-stalled ribosome is derived via molecular dynamics flexible fitting, complete with P- and A-site tRNAs. Subsequently, simulations of native and mutated SecM-stalled ribosomes have been carried out to investigate possible interaction pathways between a critical SecM residue, R163, and the PTC. The simulations reveal, in particular, the role of SecM in altering the position of the tRNAs in the ribosome, thus demonstrating how the presence of SecM in the exit tunnel induces stalling. Finally, steered molecular dynamics simulations pulling SecM towards the tunnel exit suggest how SecA interacting with SecM from outside the ribosome relieves stalling.


Download Full Text

The manuscripts available on our site are provided for your personal use only and may not be retransmitted or redistributed without written permissions from the paper's publisher and author. You may not upload any of this site's material to any public server, on-line service, network, or bulletin board without prior written permission from the publisher and author. You may not make copies for any commercial purpose. Reproduction or storage of materials retrieved from this web site is subject to the U.S. Copyright Act of 1976, Title 17 U.S.C.

Download full text: PDF (918.6KB), Supplemental Material ( 2.5MB) - Supplementary PDF, Journal