The tRNA synthetase paralog PoxA modifies elongation factor-P with (R)-β-lysine

Roy, Hervé; Zou, Shengwei; Bullwinkle, Tammy J.; Wolfe, Benjamin Scott; Gilreath, Marla S.; Forsyth, Craig J.; Navarre, William Wiley; Ibba, Michael

doi:10.1038/nchembio.632

Cited by 88 publications

(110 citation statements)

References 24 publications

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“…Our data show that the absence of YfcM does not phenocopy loss of EF-P, PoxA, or YjeK. These results strongly suggest that YfcM is not a critical component of the modification pathway necessary for EF-P activity in vivo (8,9). Although not essential for EF-P activation, hydroxylation further stimulated puromycin reactivity, suggesting that it may function to modulate EF-P activity.…”

Section: Discussionmentioning

confidence: 65%

“…EF-P is similar in size and shape to a tRNA and can be post-translationally modified by a lysyl-tRNA synthetase paralog, PoxA (7,8). In a reaction analogous to tRNA aminoacylation, PoxA activates (R)-␤-lysine and subsequently transfers it to a conserved residue (Lys-34) in EF-P (9). Attachment of a ␤-lysyl moiety is necessary for EF-P functionality both in vivo and in vitro (2,8).…”

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confidence: 99%

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(R)-β-Lysine-modified Elongation Factor P Functions in Translation Elongation

Bullwinkle

Zou

Rajkovic

et al. 2013

Journal of Biological Chemistry

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Background: Post-translational modification activates bacterial elongation factor P (EF-P) in several Gram-negative bacteria.Results: The addition of ␤-lysine alone is sufficient for activation of EF-P to function in translation. Conclusion: Modified EF-P acts by regulating translation of a subset of mRNAs. Significance: EF-P can post-transcriptionally regulate gene expression by controlling translation elongation.

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Section: Discussionmentioning

confidence: 65%

mentioning

confidence: 99%

(R)-β-Lysine-modified Elongation Factor P Functions in Translation Elongation

Bullwinkle

Zou

Rajkovic

et al. 2013

Journal of Biological Chemistry

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“…Our recent work determined that two enzymes, PoxA and YjeK, coordinately modify EF-P in a manner analogous to the modification of aIF5A and eIF5A with hypusine (42,48). Notably, the modification of EF-P occurs at a lysyl residue (lysine 34) that corresponds to the same position as the lysyl residue that is converted to hypusine in aIF5A and eIF5A.…”

mentioning

confidence: 99%

“…While PoxA bears close homology to the catalytic domain of the class II lysyl-tRNA synthetase (LysRS) family of enzymes that catalyze the addition of lysine to its cognate tRNA Lys , a number of studies have failed to show that PoxA can aminoacylate a tRNA (1,36,37). PoxA instead catalyzes the ligation of (R)-␤-lysine to the side chain of the conserved lysyl residue in EF-P to yield an unusual lysyl-␤-lysine moiety (42,48,60). Salmonella poxA and yjeK mutants display nearly identical phenotypes, including increased resistance to S-nitrosoglutathione (GSNO) and hypersusceptibility to a large number of unrelated antimicrobial compounds (7,42,55).…”

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confidence: 99%

Loss of Elongation Factor P Disrupts Bacterial Outer Membrane Integrity

et al. 2012

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Elongation factor P (EF-P) is posttranslationally modified at a conserved lysyl residue by the coordinated action of two enzymes, PoxA and YjeK. We have previously established the importance of this modification in Salmonella stress resistance. Here we report that, like poxA and yjeK mutants, Salmonella strains lacking EF-P display increased susceptibility to hypoosmotic conditions, antibiotics, and detergents and enhanced resistance to the compound S-nitrosoglutathione. The susceptibility phenotypes are largely explained by the enhanced membrane permeability of the efp mutant, which exhibits increased uptake of the hydrophobic dye 1-N-phenylnaphthylamine (NPN). Analysis of the membrane proteomes of wild-type and efp mutant Salmonella strains reveals few changes, including the prominent overexpression of a single porin, KdgM, in the efp mutant outer membrane. Removal of KdgM in the efp mutant background ameliorates the detergent, antibiotic, and osmosensitivity phenotypes and restores wild-type permeability to NPN. Our data support a role for EF-P in the translational regulation of a limited number of proteins that, when perturbed, renders the cell susceptible to stress by the adventitious overexpression of an outer membrane porin.

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“…(S)-α-lysine. [126] The crystal structure of the B. diazoefficiens homologue ( Figure 1C) showed that the structure of the homologue is remarkably similar to the atypical M. barkeri SerRS, although they share a weak sequence similarity (15 % identity). [122] The structure of B. diazoefficiens homologue recapitulates the structure of M. barkeri SerRS catalytic domain, with very few differences within and close to the active site.…”

Section: Amino Acid Activation By Serrs Homologuesmentioning

confidence: 94%

Seryl-tRNA Synthetases in Translation and Beyond

Močibob¹,

Rokov-Plavec²,

Godinić-Mikulčić³

et al. 2016

Croat. Chem. Acta

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Abstract:For a long time seryl-tRNA synthetases (SerRSs) stood as an archetypal, canonical aminoacyl-tRNA synthetases (aaRS), exhibiting only basic tRNA aminoacylation activity and with no moonlighting functions beyond protein biosynthesis. The picture has changed substantially in recent years after the discovery that SerRSs play an important role in antibiotic production and resistance and act as a regulatory factor in vascular development, as well as after the discovery of mitochondrial morphogenesis factor homologous to SerRS in insects. In this review we summarize the recent research results from our laboratory, which advance the understanding of seryl-tRNA synthetases and further paint the dynamic picture of unexpected SerRS activities. SerRS from archaeon Methanothermobacter thermautotrophicus was shown to interact with the large ribosomal subunit and it was postulated to contribute to a more efficient translation by the"tRNA channeling" hypothesis. Discovery of the atypical SerRS in a small number of methanogenic archaea led to the discovery of a new family of enzymes in numerous bacteria -amino acid:[carrier protein] ligases (aa:CP ligases). These SerRS homologues resigned tRNA aminoacylation activity, and instead adopted carrier proteins as the acceptors of activated amino acids. The crystal structure of the aa:CP ligase complex with the carrier protein revealed that the interactions between two macromolecules are incomparable to tRNA binding by the aaRS and consequently represent a true evolutionary invention. Kinetic investigations of SerRSs and the accuracy of amino acid selection revealed that SerRSs possess pre-transfer proofreading activity, challenging the widely accepted presumption that hydrolytic proofreading activity must reside in an additional, separate editing domain, not present in SerRSs. Finally, the plant tRNA serylation system is discussed, which is particularly interesting due to the fact that protein biosynthesis takes place in three cellular compartments: cytosol, mitochondria and chloroplasts. Plant cytosolic SerRSs showed broad tRNA Ser specificity and flexibility, unlike SerRSs from other organisms. High fidelity of SerRS dually targeted to mitochondria and chloroplasts indicated its importance in plant organellar quality control.

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The tRNA synthetase paralog PoxA modifies elongation factor-P with (R)-β-lysine

Cited by 88 publications

References 24 publications

(R)-β-Lysine-modified Elongation Factor P Functions in Translation Elongation

(R)-β-Lysine-modified Elongation Factor P Functions in Translation Elongation

Loss of Elongation Factor P Disrupts Bacterial Outer Membrane Integrity

Seryl-tRNA Synthetases in Translation and Beyond

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