Bulletin of the American Physical Society
APS March Meeting 2018
Monday–Friday, March 5–9, 2018; Los Angeles, California
Session L60: Poster Session II
Wednesday, March 7, 2018
LACC Room: West Hall A
Abstract: L60.00257 : Mechanism of force-induced restarting of protein synthesis in SecM-stalled ribosomes
Stalling peptides are a class of proteins that induce long-timescale pauses in ribosomal translation as they are synthesized. Since this stalling can be relieved with a physical force applied to the end of the nascent protein, they have been utilized as force sensors for biological processes. Despite their utility, the mechanism through which an applied force leads to the restart of synthesis is still unclear. We run molecular dynamics simulations of a stalling peptide in the ribosome exit tunnel. By directly applying a force to the end of the peptide, we are able to characterize several intermediate states in the stall breaking pathway. Identification of these states allows for the rational design of stalling peptides sensitive to different force ranges. Through repeated measurements of the forces required to induce transitions between these states, we characterize the free energy landscape of the stall, and use it to make predictions about stall-breaking as it occurs in experimentally realistic force-regimes and timescales.
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