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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/25831

Title: Phosphorylation decelerates conformational dynamics in bacterial translation elongation factors
Authors: Talavera, Ariel
Hendrix, Jelle
Versees, Wim
Jurenas, 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
Issue Date: 2018
Publisher: AMER ASSOC ADVANCEMENT SCIENCE
Citation: SCIENCE ADVANCES, 4(3) (Art N° eaap9714)
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 beta-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.
Notes: [Talavera, Ariel; Versees, Wim; Singh, Ranjan Kumar; Konijnenberg, Albert; De Gieter, Steven; De Greve, Henri; Loris, Remy] Vrije Univ Brussel, Dept Bioengn Sci, Struct Biol Brussels, Brussels, Belgium. [Talavera, Ariel; Versees, Wim; Singh, Ranjan Kumar; Konijnenberg, Albert; De Gieter, Steven; De Greve, Henri; Loris, Remy] VIB, Ctr Struct Biol, Flanders, Belgium. [Hendrix, Jelle; Vandenberk, Niels; Hofkens, Johan] Univ Leuven, Mol Imaging & Photon, B-3001 Leuven, Belgium. [Hendrix, Jelle] Hasselt Univ, Biomed Res Inst, B-3590 Hasselt, Belgium. [Jurenas, Dukas; Van Nerom, Katleen; Garcia-Pino, Abel] Univ Libre Bruxelles, Dept Mol Biol, Cellular & Mol Microbiol, Brussels, Belgium. [Konijnenberg, Albert; Sobott, Frank] Univ Antwerp, Dept Chem, Biomol & Analyt Mass Spectrometry Grp, Antwerp, Belgium. [Castro-Roa, Daniel; Zenkin, Nikolay] Newcastle Univ, Inst Cell & Mol Biosci, Ctr Bacterial Cell Biol, Baddiley Clark Bldg,Richardson Rd, Newcastle Upon Tyne NE2 4AX, Tyne & Wear, England. [Barth, Anders] Ludwig Maximilians Univ Munchen, Dept Chem & Pharm, Fluorescence Applicat Biol Lab, Munich, Germany. [Sobott, Frank] Univ Leeds, Sch Mol & Cellular Biol, Leeds LS2 9JT, W Yorkshire, England. [Sobott, Frank] Univ Leeds, Astbury Ctr Struct Mol Biol, Leeds LS2 9JT, W Yorkshire, England. [Hofkens, Johan] Univ Copenhagen, Dept Chem, Nanosci Ctr, Univ Pk 5, DK-2100 Copenhagen, Denmark.
URI: http://hdl.handle.net/1942/25831
DOI: 10.1126/sciadv.aap9714
ISI #: 000427892700026
ISSN: 2375-2548
Category: A1
Type: Journal Contribution
Appears in Collections: Research publications

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