scholarly journals Translation elongation factor P (EF-P)

2020 ◽  
Vol 44 (2) ◽  
pp. 208-218 ◽  
Author(s):  
Katherine R Hummels ◽  
Daniel B Kearns
Keyword(s):  
Elongation Factor ◽  
Peptide Bond ◽  
Post Translational Modification ◽  
Translation Elongation Factor ◽  
Translation Elongation ◽  
Isolation And Characterization ◽  
Domains Of Life ◽  
Ribosome Pausing ◽  
Elongation Factor P

ABSTRACT Translation elongation factor P (EF-P) is conserved in all three domains of life (called eIF5A and aIF5A in eukaryotes and archaea, respectively) and functions to alleviate ribosome pausing during the translation of specific sequences, including consecutive proline residues. EF-P was identified in 1975 as a factor that stimulated the peptidyltransferase reaction in vitro but its involvement in the translation of tandem proline residues was not uncovered until 2013. Throughout the four decades of EF-P research, perceptions of EF-P function have changed dramatically. In particular, while EF-P was thought to potentiate the formation of the first peptide bond in a protein, it is now broadly accepted to act throughout translation elongation. Further, EF-P was initially reported to be essential, but recent work has shown that the requirement of EF-P for growth is conditional. Finally, it is thought that post-translational modification of EF-P is strictly required for its function but recent studies suggest that EF-P modification may play a more nuanced role in EF-P activity. Here, we review the history of EF-P research, with an emphasis on its initial isolation and characterization as well as the discoveries that altered our perceptions of its function.

scholarly journals Switching the Post-translational Modification of Translation Elongation Factor EF-P

2019 ◽  
Vol 10 ◽  
Author(s):  
Wolfram Volkwein ◽  
Ralph Krafczyk ◽  
Pravin Kumar Ankush Jagtap ◽  
Marina Parr ◽  
Elena Mankina ◽  
...  
Keyword(s):  
Elongation Factor ◽  
Post Translational Modification ◽  
Translation Elongation Factor ◽  
Translation Elongation

scholarly journals Mapping the human translation elongation factor eEF1H complex using the yeast two-hybrid system

2002 ◽  
Vol 365 (3) ◽  
pp. 669-676 ◽  
Author(s):  
Francisco MANSILLA ◽  
Irene FRIIS ◽  
Mandana JADIDI ◽  
Karen M. NIELSEN ◽  
Brian F.C. CLARK ◽  
...  
Keyword(s):  
Elongation Factor ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Translation Elongation Factor ◽  
Yeast Two Hybrid ◽  
Translation Elongation ◽  
Guanine Nucleotide Exchange ◽  
Yeast Two Hybrid System ◽  
Two Hybrid

In eukaryotes, the eukaryotic translation elongation factor eEF1A responsible for transporting amino-acylated tRNA to the ribosome forms a higher-order complex, eEF1H, with its guanine-nucleotide-exchange factor eEF1B. In metazoans, eEF1B consists of three subunits: eEF1Bα, eEF1Bβ and eEF1Bγ. The first two subunits possess the nucleotide-exchange activity, whereas the role of the last remains poorly defined. In mammals, two active tissue-specific isoforms of eEF1A have been identified. The reason for this pattern of differential expression is unknown. Several models on the basis of in vitro experiments have been proposed for the macromolecular organization of the eEF1H complex. However, these models differ in various aspects. This might be due to the difficulties of handling, particularly the eEF1Bβ and eEF1Bγ subunits in vitro. Here, the human eEF1H complex is for the first time mapped using the yeast two-hybrid system, which is a powerful in vivo technique for analysing protein—protein interactions. The following complexes were observed: eEF1A1:eEF1Bα, eEF1A1:eEF1Bβ, eEF1Bβ:eEF1Bβ, eEF1Bα:eEF1Bγ, eEF1Bβ:eEF1Bγ and eEF1Bα:eEF1Bγ:eEF1Bβ, where the last was observed using a three-hybrid approach. Surprisingly, eEF1A2 showed no or only little affinity for the guanine-nucleotide-exchange factors. Truncated versions of the subunits of eEF1B were used to orientate these subunits within the resulting model. The model unit is a pentamer composed of two molecules of eEF1A, each interacting with either eEF1Bα or eEF1Bβ held together by eEF1Bγ. These units can dimerize via eEF1Bβ. Our model is compared with other models, and structural as well as functional aspects of the model are discussed.

scholarly journals Arginine-rhamnosylation as new strategy to activate translation elongation factor P

2015 ◽  
Vol 11 (4) ◽  
pp. 266-270 ◽  
Author(s):  
Jürgen Lassak ◽  
Eva C Keilhauer ◽  
Maximilian Fürst ◽  
Kristin Wuichet ◽  
Julia Gödeke ◽  
...  
Keyword(s):  
Elongation Factor ◽  
Translation Elongation Factor ◽  
Translation Elongation ◽  
New Strategy ◽  
Elongation Factor P

scholarly journals Elongation Factor P Interactions with the Ribosome Are Independent of Pausing

mBio ◽  
2017 ◽  
Vol 8 (4) ◽  
Author(s):  
Rodney Tollerson ◽  
Anne Witzky ◽  
Michael Ibba
Keyword(s):  
Single Molecule ◽  
Bond Formation ◽  
Elongation Factor ◽  
Peptide Bond ◽  
Cellular Distribution ◽  
Peptide Bond Formation ◽  
Translation Elongation ◽  
Single Molecule Tracking ◽  
Localization Pattern ◽  
Elongation Factor P

ABSTRACT Bacterial elongation factor P (EF-P) plays a pivotal role in the translation of polyproline motifs. To stimulate peptide bond formation, EF-P must enter the ribosome via an empty E-site. Using fluorescence-based single-molecule tracking, Mohapatra et al. (S. Mohapatra, H. Choi, X. Ge, S. Sanyal, and J. C. Weisshaar, mBio 8:e00300-17, 2017, https://doi.org/10.1128/mBio.00300-17 !) monitored the cellular distribution of EF-P and quantified the frequency of association between EF-P and the ribosome under various conditions. Findings from the study showed that EF-P has a localization pattern that is strikingly similar to that of ribosomes. Intriguingly, EF-P was seen to bind ribosomes more frequently than the estimated number of pausing events, indicating that E-site vacancies occur even when ribosomes are not paused. The study provides new insights into the mechanism of EF-P-dependent peptide bond formation and the intricacies of translation elongation.

scholarly journals Comparison of the ability of mammalian eEF1A1 and its oncogenic variant eEF1A2 to interact with actin and calmodulin

2017 ◽  
Vol 398 (1) ◽  
pp. 113-124 ◽  
Author(s):  
Oleksandra Novosylna ◽  
Annette Doyle ◽  
Dmytro Vlasenko ◽  
Mark Murphy ◽  
Boris Negrutskii ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Elongation Factor ◽  
Translation Elongation Factor ◽  
Translation Elongation ◽  
Oncogenic Potential ◽  
Regulatory Systems ◽  
Protein Variants ◽  
Homologous Tissue ◽  
Trna Binding

Abstract The question as to why a protein exerts oncogenic properties is answered mainly by well-established ideas that these proteins interfere with cellular signaling pathways. However, the knowledge about structural and functional peculiarities of the oncoproteins causing these effects is far from comprehensive. The 97.5% homologous tissue-specific A1 and A2 isoforms of mammalian translation elongation factor eEF1A represent an interesting model to study a difference between protein variants of a family that differ in oncogenic potential. We propose that the different oncogenic impact of A1 and A2 might be explained by differences in their ability to communicate with their respective cellular partners. Here we probed this hypothesis by studying the interaction of eEF1A with two known partners – calmodulin and actin. Indeed, an inability of the A2 isoform to interact with calmodulin is shown, while calmodulin is capable of binding A1 and interferes with its tRNA-binding and actin-bundling activities in vitro. Both A1 and A2 variants revealed actin-bundling activity; however, the form of bundles formed in the presence of A1 or A2 was distinctly different. Thus, a potential inability of A2 to be controlled by Ca2+-mediated regulatory systems is revealed.

scholarly journals Translation Elongation Factor EF-Tu Modulates Filament Formation of Actin-Like MreB Protein In Vitro

2015 ◽  
Vol 427 (8) ◽  
pp. 1715-1727 ◽  
Author(s):  
Hervé Joël Defeu Soufo ◽  
Christian Reimold ◽  
Hannes Breddermann ◽  
Hans G. Mannherz ◽  
Peter L. Graumann
Keyword(s):  
Elongation Factor ◽  
Filament Formation ◽  
Translation Elongation Factor ◽  
Translation Elongation

scholarly journals Overexpression of Translation Elongation Factor 1A Affects the Organization and Function of the Actin Cytoskeleton in Yeast

Genetics ◽  
2001 ◽  
Vol 157 (4) ◽  
pp. 1425-1436
Author(s):  
Raj Munshi ◽  
Kimberly A Kandl ◽  
Anne Carr-Schmid ◽  
Johanna L Whitacre ◽  
Alison E M Adams ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Elongation Factor ◽  
Nucleotide Exchange ◽  
Translation Elongation Factor ◽  
Translation Elongation ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
And Function

Abstract The translation elongation factor 1 complex (eEF1) plays a central role in protein synthesis, delivering aminoacyl-tRNAs to the elongating ribosome. The eEF1A subunit, a classic G-protein, also performs roles aside from protein synthesis. The overexpression of either eEF1A or eEF1Bα, the catalytic subunit of the guanine nucleotide exchange factor, in Saccharomyces cerevisiae results in effects on cell growth. Here we demonstrate that overexpression of either factor does not affect the levels of the other subunit or the rate or accuracy of protein synthesis. Instead, the major effects in vivo appear to be at the level of cell morphology and budding. eEF1A overexpression results in dosage-dependent reduced budding and altered actin distribution and cellular morphology. In addition, the effects of excess eEF1A in actin mutant strains show synthetic growth defects, establishing a genetic connection between the two proteins. As the ability of eEF1A to bind and bundle actin is conserved in yeast, these results link the established ability of eEF1A to bind and bundle actin in vitro with nontranslational roles for the protein in vivo.

scholarly journals Structural basis for EarP-mediated arginine glycosylation of translation elongation factor EF-P

2017 ◽  
Author(s):  
Ralph Krafczyk ◽  
Jakub Macošek ◽  
Daniel Gast ◽  
Swetlana Wunder ◽  
Pravin Kumar Ankush Jagtap ◽  
...  
Keyword(s):  
Elongation Factor ◽  
Structural Data ◽  
Enzyme Characterization ◽  
Structural Basis ◽  
Translation Elongation Factor ◽  
Translation Elongation ◽  
Enzymatic Mechanism ◽  
Bacterial Translation

ABSTRACTGlycosylation is a universal strategy to post-translationally modify proteins. The recently discovered arginine rhamnosylation activates the polyproline specific bacterial translation elongation factor EF-P. EF-P is rhamnosylated on arginine 32 by the glycosyltransferase EarP. However, the enzymatic mechanism remains elusive. In the present study, we solved the crystal structure of EarP from Pseudomonas putida. The enzyme is composed of two opposing domains with Rossmann-folds, thus constituting a GT-B glycosyltransferase. While TDP-rhamnose is located within a highly conserved pocket of the C-domain, EarP recognizes the EF-P via its KOW-like N-domain. Based on our structural data combined with an in vitro /in vivo enzyme characterization, we propose a mechanism of inverting arginine glycosylation. As EarP is essential for pathogenicity in P. aeruginosa our study provides the basis for targeted inhibitor design.

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