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Lookup NU author(s): Daniel Castro-Roa, Professor Nikolay ZenkinORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Copyright © 2018 The Authors, some rights reserved. Bacterial protein synthesis is intricately connected to metabolic rate. One of the ways in which bacteria respond to environmental stress is through posttranslational modifications of translation factors. Translation elongation factor Tu (EF-Tu) is methylated and phosphorylated in response to nutrient starvation upon entering stationary phase, and its phosphorylation is a crucial step in the pathway toward sporulation. We analyze how phosphorylation leads to inactivation of Escherichia coli EF-Tu. We provide structural and biophysical evidence that phosphorylation of EF-Tu at T382 acts as an efficient switch that turns off protein synthesis by decoupling nucleotide binding from the EF-Tu conformational cycle. Direct modifications of the EF-Tu switch I region or modifications in other regions stabilizing the b-hairpin state of switch I result in an effective allosteric trap that restricts the normal dynamics of EF-Tu and enables the evasion of the control exerted by nucleotides on G proteins. These results highlight stabilization of a phosphorylation-induced conformational trap as an essential mechanism for phosphoregulation of bacterial translation and metabolism. We propose that this mechanism may lead to the multisite phosphorylation state observed during dormancy and stationary phase.
Author(s): Talavera A, Hendrix J, Versees W, Jurenas D, Van Nerom K, Vandenberk N, Singh RK, Konijnenberg A, De Gieter S, Castro-Roa D, Barth A, De Greve H, Sobott F, Hofkens J, Zenkin N, Loris R, Garcia-Pino A
Publication type: Article
Publication status: Published
Journal: Science Advances
Year: 2018
Volume: 4
Issue: 3
Online publication date: 14/03/2018
Acceptance date: 07/02/2018
Date deposited: 03/04/2018
ISSN (electronic): 2375-2548
Publisher: American Association for the Advancement of Science
URL: https://doi.org/10.1126/sciadv.aap9714
DOI: 10.1126/sciadv.aap9714
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