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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 | Source: | 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. | Document URI: | http://hdl.handle.net/1942/25831 | ISSN: | 2375-2548 | e-ISSN: | 2375-2548 | DOI: | 10.1126/sciadv.aap9714 | ISI #: | 000427892700026 | Rights: | Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2019 |
Appears in Collections: | Research publications |
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eaap9714.full.pdf | Published version | 2.39 MB | Adobe PDF | View/Open |
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