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Structural and biochemical analysis of Escherichia coli ObgE, a central regulator of bacterial persistence.

Gkekas S, Singh RK, Shkumatov AV, Messens J, Fauvart M, Verstraeten N, Michiels J, Versées W
J Biol Chem 292 5871-5883 (2017)
Cited: 12 times
EuropePMC logo PMID: 28223358

Abstract

The Obg protein family belongs to the TRAFAC (translation factor) class of P-loop GTPases and is conserved from bacteria to eukaryotes. Essential roles in many different cellular processes have been suggested for the Obg protein from Escherichia coli (ObgE), and we recently showed that it is a central regulator of bacterial persistence. Here, we report the first crystal structure of ObgE at 1.85-Å resolution in the GDP-bound state, showing the characteristic N-terminal domain and a central G domain that are common to all Obg proteins. ObgE also contains an intrinsically disordered C-terminal domain, and we show here that this domain specifically contributed to GTP binding, whereas it did not influence GDP binding or GTP hydrolysis. Biophysical analysis, using small angle X-ray scattering and multi-angle light scattering experiments, revealed that ObgE is a monomer in solution, regardless of the bound nucleotide. In contrast to recent suggestions, our biochemical analyses further indicate that ObgE is neither activated by K+ ions nor by homodimerization. However, the ObgE GTPase activity was stimulated upon binding to the ribosome, confirming the ribosome-dependent GTPase activity of the Obg family. Combined, our data represent an important step toward further unraveling the detailed molecular mechanism of ObgE, which might pave the way to further studies into how this GTPase regulates bacterial physiology, including persistence.

Reviews - 5m04 mentioned but not cited (1)

  1. The Impact of the Stringent Response on TRAFAC GTPases and Prokaryotic Ribosome Assembly. Bennison DJ, Irving SE, Corrigan RM. Cells 8 E1313 (2019)

Articles - 5m04 mentioned but not cited (3)

  1. Stepwise maturation of the peptidyl transferase region of human mitoribosomes. Lenarčič T, Jaskolowski M, Leibundgut M, Scaiola A, Schönhut T, Saurer M, Lee RG, Rackham O, Filipovska A, Ban N. Nat Commun 12 3671 (2021)
  2. Structural basis of cytokine-mediated activation of ALK family receptors. De Munck S, Provost M, Kurikawa M, Omori I, Mukohyama J, Felix J, Bloch Y, Abdel-Wahab O, Bazan JF, Yoshimi A, Savvides SN. Nature 600 143-147 (2021)
  3. Structural and biochemical analysis of Escherichia coli ObgE, a central regulator of bacterial persistence. Gkekas S, Singh RK, Shkumatov AV, Messens J, Fauvart M, Verstraeten N, Michiels J, Versées W. J Biol Chem 292 5871-5883 (2017)


Reviews citing this publication (3)

  1. Regulatory Hierarchies Controlling Virulence Gene Expression in Shigella flexneri and Vibrio cholerae. Dorman MJ, Dorman CJ. Front Microbiol 9 2686 (2018)
  2. Developmentally regulated GTPases: structure, function and roles in disease. Westrip CAE, Zhuang Q, Hall C, Eaton CD, Coleman ML. Cell Mol Life Sci 78 7219-7235 (2021)
  3. The structure-function analysis of Obg-like GTPase proteins along the evolutionary tree from bacteria to humans. Chakraborty A, Halder S, Kishore P, Saha D, Saha S, Sikder K, Basu A. Genes Cells 27 469-481 (2022)

Articles citing this publication (5)

  1. Human GTPBP5 is involved in the late stage of mitoribosome large subunit assembly. Cipullo M, Pearce SF, Lopez Sanchez IG, Gopalakrishna S, Krüger A, Schober F, Busch JD, Li X, Wredenberg A, Atanassov I, Rorbach J. Nucleic Acids Res 49 354-370 (2021)
  2. A Mutant Isoform of ObgE Causes Cell Death by Interfering with Cell Division. Dewachter L, Verstraeten N, Jennes M, Verbeelen T, Biboy J, Monteyne D, Pérez-Morga D, Verstrepen KJ, Vollmer W, Fauvart M, Michiels J. Front Microbiol 8 1193 (2017)
  3. GTP Binding is Necessary for the Activation of a Toxic Mutant Isoform of the Essential GTPase ObgE. Dewachter L, Deckers B, Martin E, Herpels P, Gkekas S, Versées W, Verstraeten N, Fauvart M, Michiels J. Int J Mol Sci 21 E16 (2019)
  4. Knockdown Experiment Reveals an Essential GTPase CgtA's Involvement in Growth, Viability, Motility, Morphology, and Persister Phenotypes in Vibrio cholerae. Das S, Chatterjee A, Datta PP. Microbiol Spectr e0318122 (2023)
  5. YbiB: a novel interactor of the GTPase ObgE. Deckers B, Vercauteren S, De Kock V, Martin C, Lazar T, Herpels P, Dewachter L, Verstraeten N, Peeters E, Ballet S, Michiels J, Michiels J, Galicia C, Versées W. Nucleic Acids Res 51 3420-3435 (2023)


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