Increased freedom of movement in the nascent chain results in dynamic changes in the structure of the SecM arrest motif

Bracken, H. A. and Woolhead, C. A. (2019) Increased freedom of movement in the nascent chain results in dynamic changes in the structure of the SecM arrest motif. Bioscience Reports, 39(1), BSR2018124. (doi:10.1042/BSR20181246) (PMID:30563926) (PMCID:PMC6340945)

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Abstract

Ribosomes are responsible for the synthesis of all cellular proteins. Due to the diversity of sequence and properties it was initially believed that translating nascent chains would travel unhindered through the ribosome exit tunnel, however a small but increasing number of proteins have been identified that interact with the exit tunnel to induce translational arrest, ( ) secretion monitor (SecM) is one such stalling peptide. How and why these peptides interact with the exit tunnel is not fully understood, however key features required for stalling appear to be an essential peptide arrest motif at the C-terminus and compaction of the nascent chain within the exit tunnel upon stalling. Mutagenesis of the SecM arrest sequence has identified three conservative point mutations that can retain a degree of stalling in this highly conserved sequence. This level of stalling is further increased when coupled with mutation of a non-essential arrest motif residue P153A. Further analysis of these mutants by pegylation assays indicates that this increase in stalling activity during translation is due to the ability of the P153A mutation to reintroduce compaction of the nascent chain within the exit tunnel possibly due to the improved flexibility of the nascent chain provided by the removal of a restrictive proline residue. The data presented here suggests that arrest sequences may be more prevalent and less highly conserved than previously thought, and highlight the significance of the interactions between the nascent chain and the exit tunnel to affecting translation arrest.

Item Type:Articles
Additional Information:HB was a recipient of a BBSRC DTP studentship
Keywords:Bacterial secretion, protein synthesis, ribosomes, translation arrest.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bracken, Miss Hazel and Woolhead, Dr Cheryl
Authors: Bracken, H. A., and Woolhead, C. A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Bioscience Reports
Publisher:Portland Press
ISSN:0144-8463
ISSN (Online):1573-4935
Published Online:18 December 2018
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Bioscience Reports 39(1): BSR2018124
Publisher Policy:Reproduced under a Creative Commons License

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