Genomes and Genes
peptide elongation factor tu
Summary: A protein found in bacteria and eukaryotic mitochondria which delivers aminoacyl-tRNA's to the A site of the ribosome. The aminoacyl-tRNA is first bound to a complex of elongation factor Tu containing a molecule of bound GTP. The resulting complex is then bound to the 70S initiation complex. Simultaneously the GTP is hydrolyzed and a Tu-GDP complex is released from the 70S ribosome. The Tu-GTP complex is regenerated from the Tu-GDP complex by the Ts elongation factor and GTP.
- Ohtsuki T, Watanabe Yi -, Takemoto C, Kawai G, Ueda T, Kita K, et al. An "elongated" translation elongation factor Tu for truncated tRNAs in nematode mitochondria. J Biol Chem. 2001;276:21571-7 pubmed
- Archambaud C, Gouin E, Pizarro Cerda J, Cossart P, Dussurget O. Translation elongation factor EF-Tu is a target for Stp, a serine-threonine phosphatase involved in virulence of Listeria monocytogenes. Mol Microbiol. 2005;56:383-96 pubmed..Accordingly, an stp deletion mutant is less sensitive to kirromycin. These results suggest an important role for Stp in regulating EF-Tu and controlling bacterial survival in the infected host. ..
- Rodnina M, Wintermeyer W. Fidelity of aminoacyl-tRNA selection on the ribosome: kinetic and structural mechanisms. Annu Rev Biochem. 2001;70:415-35 pubmed..In utilizing induced fit for substrate discrimination, the ribosome resembles other nucleic acid-programmed polymerases. ..
- Gromadski K, Wieden H, Rodnina M. Kinetic mechanism of elongation factor Ts-catalyzed nucleotide exchange in elongation factor Tu. Biochemistry. 2002;41:162-9 pubmed..At in vivo concentrations of nucleotides and factors, the overall exchange rate, as calculated from the elemental rate constants, is 30 s(-1), which is compatible with the rate of protein synthesis in the cell. ..
- Gaucher E, Miyamoto M, Benner S. Function-structure analysis of proteins using covarion-based evolutionary approaches: Elongation factors. Proc Natl Acad Sci U S A. 2001;98:548-52 pubmed..We illustrate this in the elongation factor family of proteins as a paradigm for applications of this type of analysis in functional genomics generally. ..
- Pleiss J, Uhlenbeck O. Identification of thermodynamically relevant interactions between EF-Tu and backbone elements of tRNA. J Mol Biol. 2001;308:895-905 pubmed..Some of these discrepancies may be reconciled based on the unbound structures of the protein and RNA. ..
- Gaucher E, Das U, Miyamoto M, Benner S. The crystal structure of eEF1A refines the functional predictions of an evolutionary analysis of rate changes among elongation factors. Mol Biol Evol. 2002;19:569-73 pubmed
- Asahara H, Uhlenbeck O. Predicting the binding affinities of misacylated tRNAs for Thermus thermophilus EF-Tu.GTP. Biochemistry. 2005;44:11254-61 pubmed..In addition, a survey of active misacylated suppressor tRNAs suggests that a minimal threshold of binding free energy for EF-Tu is required for suppression to occur. ..
- Cochella L, Green R. An active role for tRNA in decoding beyond codon:anticodon pairing. Science. 2005;308:1178-80 pubmed..These data provide evidence for a direct role for tRNA in signaling its own acceptance during decoding and support its fundamental role during the evolution of protein synthesis. ..
- Jeppesen M, Navratil T, Spremulli L, Nyborg J. Crystal structure of the bovine mitochondrial elongation factor Tu.Ts complex. J Biol Chem. 2005;280:5071-81 pubmed..The structure of the EF-Tumt.Tsmt complex provides new insights into the nucleotide exchange mechanism and provides a framework for explaining much of the mutational data obtained for this complex. ..
- Sanderson L, Uhlenbeck O. Exploring the specificity of bacterial elongation factor Tu for different tRNAs. Biochemistry. 2007;46:6194-200 pubmed..However, the remaining two amino acids contact tRNA at conserved positions, suggesting that more global structural or dynamic properties of the free tRNA contribute to specificity. ..
- Parmeggiani A, Nissen P. Elongation factor Tu-targeted antibiotics: four different structures, two mechanisms of action. FEBS Lett. 2006;580:4576-81 pubmed
- Andersen G, Thirup S, Spremulli L, Nyborg J. High resolution crystal structure of bovine mitochondrial EF-Tu in complex with GDP. J Mol Biol. 2000;297:421-36 pubmed..The C-terminal extension of mitochondrial EF-Tu has structural similarities with DNA recognising zinc fingers suggesting that the extension may be involved in recognition of RNA. ..
- Gromadski K, Rodnina M. Kinetic determinants of high-fidelity tRNA discrimination on the ribosome. Mol Cell. 2004;13:191-200 pubmed..tRNA selection at the initial selection step is entirely kinetically controlled and is due to much faster (650-fold) GTP hydrolysis of cognate compared to near-cognate substrate. ..
- Dallo S, Kannan T, Blaylock M, Baseman J. Elongation factor Tu and E1 beta subunit of pyruvate dehydrogenase complex act as fibronectin binding proteins in Mycoplasma pneumoniae. Mol Microbiol. 2002;46:1041-51 pubmed..These results demonstrate that M. pneumoniae EF-Tu and PDH-B, in addition to their major cytoplasmic biosynthetic and metabolic roles, can be surface translocated, which confers additional important biological functions. ..
- Spasic A, Sitha S, Korchak M, Chu S, Mohanty U. Polyelectrolyte behavior and kinetics of aminoacyl-tRNA on the ribosome. J Phys Chem B. 2008;112:4161-3 pubmed publisher..We predict the magnesium binding sites in the ternary complex at low magnesium concentration and unravel the nature of the interaction energy of magnesium with site-specific tRNAPhe bases. ..
- Schrader J, Chapman S, Uhlenbeck O. Tuning the affinity of aminoacyl-tRNA to elongation factor Tu for optimal decoding. Proc Natl Acad Sci U S A. 2011;108:5215-20 pubmed publisher..Consistent with available crystal structures, the identity of the esterified amino acid and three base pairs in the T stem of tRNA combine to define the affinity of each aa-tRNA for EF-Tu, both off and on the ribosome. ..
- Ohtsuki T, Sakurai M, Sato A, Watanabe K. Characterization of the interaction between the nucleotide exchange factor EF-Ts from nematode mitochondria and elongation factor Tu. Nucleic Acids Res. 2002;30:5444-51 pubmed..Thus, the nematode EF-Ts appears to have a broad specificity for EF-Tu molecules from different species. ..
- Poulsen M, Cafaro M, Boomsma J, Currie C. Specificity of the mutualistic association between actinomycete bacteria and two sympatric species of Acromyrmex leaf-cutting ants. Mol Ecol. 2005;14:3597-604 pubmed
- Leeds J, LaMarche M, Brewer J, Bushell S, Deng G, Dewhurst J, et al. In vitro and in vivo activities of novel, semisynthetic thiopeptide inhibitors of bacterial elongation factor Tu. Antimicrob Agents Chemother. 2011;55:5277-83 pubmed publisher..23 mg/kg, respectively. In summary, compounds 1 and 2 are active in vitro and in vivo activity against difficult-to-treat Gram-positive bacterial infections and represent a promising new class of antibacterials for use in human therapy. ..
- Schmeing T, Voorhees R, Kelley A, Gao Y, Murphy F, Weir J, et al. The crystal structure of the ribosome bound to EF-Tu and aminoacyl-tRNA. Science. 2009;326:688-694 pubmed publisher..A series of conformational changes in EF-Tu and aminoacyl-tRNA suggests a communication pathway between the decoding center and the guanosine triphosphatase center of EF-Tu. ..
- Cetin R, Anborgh P, Cool R, Parmeggiani A. Functional role of the noncatalytic domains of elongation factor Tu in the interactions with ligands. Biochemistry. 1998;37:486-95 pubmed
- Ticu C, Nechifor R, Nguyen B, Desrosiers M, Wilson K. Conformational changes in switch I of EF-G drive its directional cycling on and off the ribosome. EMBO J. 2009;28:2053-65 pubmed publisher..Collectively, our results support a central role of sw1 in driving the EF-G cycle during protein synthesis. ..
- Manchester K. Determination of the kinetics of guanine nucleotide exchange on EF-Tu and EF-Ts: continuing uncertainties. Biochem Biophys Res Commun. 2004;314:1-5 pubmed..Metabolic control analysis has been applied to determine the degree of flux control of the different steps in the pathway. ..
- Barel M, Hovanessian A, Meibom K, Briand J, Dupuis M, Charbit A. A novel receptor - ligand pathway for entry of Francisella tularensis in monocyte-like THP-1 cells: interaction between surface nucleolin and bacterial elongation factor Tu. BMC Microbiol. 2008;8:145 pubmed publisher..Thus, the use of either nucleolin-specific pseudopeptide HB-19 or recombinant EF-Tu could provide attractive therapeutic approaches for modulating F. tularensis infection. ..
- Balasubramanian S, Kannan T, Baseman J. The surface-exposed carboxyl region of Mycoplasma pneumoniae elongation factor Tu interacts with fibronectin. Infect Immun. 2008;76:3116-23 pubmed publisher..These observations highlight the unique, multifaceted, and unpredictable role of the classically defined cytoplasmic protein EF-Tu relative to cellular function, compartmentalization, and topography. ..
- Kavaliauskas D, Nissen P, Knudsen C. The busiest of all ribosomal assistants: elongation factor Tu. Biochemistry. 2012;51:2642-51 pubmed publisher..In bacteria, elongation factor Tu plays a central role during the selection of the correct amino acids throughout the elongation phase of translation. Elongation factor Tu is the main subject of this review. ..
- Dallo S, Zhang B, Denno J, Hong S, Tsai A, Haskins W, et al. Association of Acinetobacter baumannii EF-Tu with cell surface, outer membrane vesicles, and fibronectin. ScientificWorldJournal. 2012;2012:128705 pubmed publisher..Altogether, with a novel combination of immunological, proteomical, and biophysical assays, these results suggest association of A. baumannii EF-Tu with the bacterial cell surface, OMVs, and fibronectin. ..
- Ito K, Ebihara K, Nakamura Y. The stretch of C-terminal acidic amino acids of translational release factor eRF1 is a primary binding site for eRF3 of fission yeast. RNA. 1998;4:958-72 pubmed..These results cannot be accounted for by the simple "eRF3-EF-Tu mimicry" model, but may provide new insight into the eRF3 function for translation termination in eukaryotes. ..
- Saarma U, Remme J, Ehrenberg M, Bilgin N. An A to U transversion at position 1067 of 23 S rRNA from Escherichia coli impairs EF-Tu and EF-G function. J Mol Biol. 1997;272:327-35 pubmed..With support from these new data we propose that nucleotide 1067 is part of the ribosomal A-site where it directly interacts with both EF-G and EF-Tu. ..
- Sanderson L, Uhlenbeck O. The 51-63 base pair of tRNA confers specificity for binding by EF-Tu. RNA. 2007;13:835-40 pubmed..While this contact is an important specificity determinant, it is clear that others remain to be identified. ..
- Sergiev P, Bogdanov A, Dontsova O. How can elongation factors EF-G and EF-Tu discriminate the functional state of the ribosome using the same binding site?. FEBS Lett. 2005;579:5439-42 pubmed..The mutual locations of these helices and GTP-binding sites in the structures of EF-Tu and EF-G are different. Thus, the orientation of the GAC relative to the SRL determines whether EF-G or EF-Tu will bind to the ribosome. ..
- Sakurai M, Ohtsuki T, Watanabe K. Modification at position 9 with 1-methyladenosine is crucial for structure and function of nematode mitochondrial tRNAs lacking the entire T-arm. Nucleic Acids Res. 2005;33:1653-61 pubmed..Thus, m1A9 is indispensable for the structure and function of T-armless tRNAs of nematode mitochondrial origin. ..
- Stortchevoi A, Varshney U, RajBhandary U. Common location of determinants in initiator transfer RNAs for initiator-elongator discrimination in bacteria and in eukaryotes. J Biol Chem. 2003;278:17672-9 pubmed..Other results show a large effect of the amino acid attached to a tRNA, glutamine versus methionine, on the binding affinity toward EF-Tu.GTP and on the stability of the EF-Tu.GTP.aminoacyl-tRNA ternary complex. ..
- Schuette J, Murphy F, Kelley A, Weir J, Giesebrecht J, Connell S, et al. GTPase activation of elongation factor EF-Tu by the ribosome during decoding. EMBO J. 2009;28:755-65 pubmed publisher..Thus, the structure provides insights into the molecular mechanism of signalling codon recognition from the decoding centre of the 30S subunit to the GTPase centre of EF-Tu. ..
- Daviter T, Wieden H, Rodnina M. Essential role of histidine 84 in elongation factor Tu for the chemical step of GTP hydrolysis on the ribosome. J Mol Biol. 2003;332:689-99 pubmed..We propose that the catalytic role of His84 is to stabilize the transition state of GTP hydrolysis by hydrogen bonding to the attacking water molecule or, possibly, the gamma-phosphate group of GTP. ..
- Roy H, Ibba M. RNA-dependent lipid remodeling by bacterial multiple peptide resistance factors. Proc Natl Acad Sci U S A. 2008;105:4667-72 pubmed publisher..Taken together, our findings reveal how the MprF proteins provide a potent virulence mechanism by which pathogens can readily acquire resistance to chemically diverse antibiotics. ..
- Martineau F, Picard F, Ke D, Paradis S, Roy P, Ouellette M, et al. Development of a PCR assay for identification of staphylococci at genus and species levels. J Clin Microbiol. 2001;39:2541-7 pubmed..aureus, S. epidermidis, S. haemolyticus, S. hominis, or S. saprophyticus) capture probes hybridizing to the 370-bp amplicon. In conclusion, this PCR assay is suitable for detection of staphylococci at both genus and species levels. ..
- Granato D, Bergonzelli G, Pridmore R, Marvin L, Rouvet M, Corthésy Theulaz I. Cell surface-associated elongation factor Tu mediates the attachment of Lactobacillus johnsonii NCC533 (La1) to human intestinal cells and mucins. Infect Immun. 2004;72:2160-9 pubmed..Our in vitro results indicate that EF-Tu, through its binding to the intestinal mucosa, might participate in gut homeostasis. ..
- Ling J, So B, Yadavalli S, Roy H, Shoji S, Fredrick K, et al. Resampling and editing of mischarged tRNA prior to translation elongation. Mol Cell. 2009;33:654-60 pubmed publisher..Resampling of mischarged tRNAs was shown to increase the accuracy of translation over ten fold during in vitro protein synthesis, supporting the presence of an additional quality control step prior to translation elongation. ..
- Hogg T, Mesters J, Hilgenfeld R. Inhibitory mechanisms of antibiotics targeting elongation factor Tu. Curr Protein Pept Sci. 2002;3:121-31 pubmed
- Balasubramanian S, Kannan T, Hart P, Baseman J. Amino acid changes in elongation factor Tu of Mycoplasma pneumoniae and Mycoplasma genitalium influence fibronectin binding. Infect Immun. 2009;77:3533-41 pubmed publisher..pneumoniae cell binding to Fn. In contrast, EF-Tu(Mg) 340-358 peptides exhibited minimal blocking activity, reinforcing the specificity of EF-Tu-Fn interactions as mediators of microbial colonization and tissue tropism...
- Carpaij N, Willems R, Bonten M, Fluit A. Comparison of the identification of coagulase-negative staphylococci by matrix-assisted laser desorption ionization time-of-flight mass spectrometry and tuf sequencing. Eur J Clin Microbiol Infect Dis. 2011;30:1169-72 pubmed publisher..The study also identified an unexpectedly high number of cases of Staphylococcus capitis infections among 62 consecutive CoNS isolates in 2009 at the University Medical Center Utrecht, the Netherlands. ..
- Ogle J, Brodersen D, Clemons W, Tarry M, Carter A, Ramakrishnan V. Recognition of cognate transfer RNA by the 30S ribosomal subunit. Science. 2001;292:897-902 pubmed..The third, or "wobble," position of the codon is free to accommodate certain noncanonical base pairs. By partially inducing these structural changes, paromomycin facilitates binding of near-cognate tRNAs. ..
- Sanderson L, Uhlenbeck O. Directed mutagenesis identifies amino acid residues involved in elongation factor Tu binding to yeast Phe-tRNAPhe. J Mol Biol. 2007;368:119-30 pubmed publisher..0 A) movements in the amino acid side-chains. Thus, despite the non-physiological crystallization conditions and crystal lattice interactions, the crystal structures reflect the biochemically relevant interaction in solution...
- Zipfel C, Kunze G, Chinchilla D, Caniard A, Jones J, Boller T, et al. Perception of the bacterial PAMP EF-Tu by the receptor EFR restricts Agrobacterium-mediated transformation. Cell. 2006;125:749-60 pubmed..These results demonstrate that EFR is the EF-Tu receptor and that plant defense responses induced by PAMPs such as EF-Tu reduce transformation by Agrobacterium. ..
- Asahara H, Uhlenbeck O. The tRNA specificity of Thermus thermophilus EF-Tu. Proc Natl Acad Sci U S A. 2002;99:3499-504 pubmed..Because EF-Tu is known to contact only the phosphodiester backbone of tRNA, the observed specificity must be a consequence of an indirect readout mechanism. ..
- Lariviere F, Wolfson A, Uhlenbeck O. Uniform binding of aminoacyl-tRNAs to elongation factor Tu by thermodynamic compensation. Science. 2001;294:165-8 pubmed..Because certain misacylated tRNAs bind EF-Tu significantly more strongly or weakly than cognate aa-tRNAs, EF-Tu may contribute to translational accuracy. ..
- Song H, Parsons M, Rowsell S, Leonard G, Phillips S. Crystal structure of intact elongation factor EF-Tu from Escherichia coli in GDP conformation at 2.05 A resolution. J Mol Biol. 1999;285:1245-56 pubmed..Comparisons of the Mg2+ binding site with other guanine nucleotide binding proteins in GDP-bound forms show that the Mg2+ co-ordination patterns are well preserved among these structures. ..