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Phosphorylation decelerates conformational dynamics in bacterial translation elongation factors

Lookup NU author(s): Daniel Castro-Roa, Professor Nikolay Zenkin

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

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.


Publication metadata

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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