Standard

Phosphorylation decelerates conformational dynamics in bacterial translation elongation factors. / Talavera, Ariel; Hendrix, Jelle; Versées, Wim; Jurėnas, Dukas; Van Nerom, Katleen; Vandenberk, Niels; Singh, Ranjan Kumar; Konijnenberg, Albert; De Gieter, Steven; Castro-Roa, Daniel; Barth, Anders; De Greve, Henri; Sobott, Frank; Hofkens, Johan; Zenkin, Nikolay; Loris, Remy; Garcia-Pino, Abel.

In: Science Advances, Vol. 4, No. 3, eaap9714, 03.2018.

Research output: Contribution to journalArticle

Harvard

Talavera, A, Hendrix, J, Versées, W, Jurėnas, 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 2018, 'Phosphorylation decelerates conformational dynamics in bacterial translation elongation factors', Science Advances, vol. 4, no. 3, eaap9714. https://doi.org/10.1126/sciadv.aap9714

APA

Vancouver

Author

Talavera, Ariel ; Hendrix, Jelle ; Versées, Wim ; Jurėnas, Dukas ; Van Nerom, Katleen ; Vandenberk, Niels ; Singh, Ranjan Kumar ; Konijnenberg, Albert ; De Gieter, Steven ; Castro-Roa, Daniel ; Barth, Anders ; De Greve, Henri ; Sobott, Frank ; Hofkens, Johan ; Zenkin, Nikolay ; Loris, Remy ; Garcia-Pino, Abel. / Phosphorylation decelerates conformational dynamics in bacterial translation elongation factors. In: Science Advances. 2018 ; Vol. 4, No. 3.

BibTeX

@article{1cfe17c01c854311b3d3409900e45ec1,
title = "Phosphorylation decelerates conformational dynamics in bacterial translation elongation factors",
abstract = "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.",
keywords = "Bacterial dormancy, persistence, Elongation factor Tu, protein phosphorylation, structural biology, molecular microbiology, molecular biophysics",
author = "Ariel Talavera and Jelle Hendrix and Wim Vers{\'e}es and Dukas Jurėnas and {Van Nerom}, Katleen and Niels Vandenberk and Singh, {Ranjan Kumar} and Albert Konijnenberg and {De Gieter}, Steven and Daniel Castro-Roa and Anders Barth and {De Greve}, Henri and Frank Sobott and Johan Hofkens and Nikolay Zenkin and Remy Loris and Abel Garcia-Pino",
year = "2018",
month = "3",
doi = "10.1126/sciadv.aap9714",
language = "English",
volume = "4",
journal = "Science Advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "3",

}

RIS

TY - JOUR

T1 - Phosphorylation decelerates conformational dynamics in bacterial translation elongation factors

AU - Talavera, Ariel

AU - Hendrix, Jelle

AU - Versées, Wim

AU - Jurėnas, Dukas

AU - Van Nerom, Katleen

AU - Vandenberk, Niels

AU - Singh, Ranjan Kumar

AU - Konijnenberg, Albert

AU - De Gieter, Steven

AU - Castro-Roa, Daniel

AU - Barth, Anders

AU - De Greve, Henri

AU - Sobott, Frank

AU - Hofkens, Johan

AU - Zenkin, Nikolay

AU - Loris, Remy

AU - Garcia-Pino, Abel

PY - 2018/3

Y1 - 2018/3

N2 - 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.

AB - 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.

KW - Bacterial dormancy

KW - persistence

KW - Elongation factor Tu

KW - protein phosphorylation

KW - structural biology

KW - molecular microbiology

KW - molecular biophysics

UR - http://www.scopus.com/inward/record.url?scp=85043995348&partnerID=8YFLogxK

U2 - 10.1126/sciadv.aap9714

DO - 10.1126/sciadv.aap9714

M3 - Article

C2 - 29546243

VL - 4

JO - Science Advances

JF - Science Advances

SN - 2375-2548

IS - 3

M1 - eaap9714

ER -

ID: 36984419