Disease relevance of TUFM

• The EFG1-mutant patient had early-onset Leigh syndrome, whereas the EFTu-mutant patient had severe infantile macrocystic leukodystrophy with micropolygyria [1].
• Due to their presence in Dane particles and the expression of a polyalbumin receptor, the immune responses against P39 and P43 may have significance in infection with hepatitis B virus and its immunoprophylaxis [2].
• Strains of E. coli harbouring mutant species of the elongation factor EF-Tu suppress the nonsense codons UAG, UAA and UGA [3].
• The depletion of EF-Tu is at least partly responsible for the inhibition of translation and the phage exclusion [4].
• Nucleotide sequence of Mycobacterium leprae elongation factor (EF-Tu) gene [5].

High impact information on TUFM

• The ribosome discriminates between correct and incorrect aminoacyl-tRNAs (aa-tRNAs), or their complexes with elongation factor Tu (EF-Tu) and GTP, according to the match between anticodon and mRNA codon in the A site [6].
• The topological order of secondary structure elements is the same as that of the guanine-nucleotide-binding domain of bacterial elongation factor EF-Tu [7].
• In the elongation cycle of bacterial protein biosynthesis, the binding of aminoacyl-tRNA (aa-tRNA) to the A-site of mRNA-programmed ribosomes is mediated by elongation factor Tu (EF-Tu) and associated with the hydrolysis of GTP [8].
• Why do two EF-Tu molecules act in the elongation cycle of protein biosynthesis [8]?
• To investigate the structure-function relationships of EF-Tu, which is widely used as a model protein, Val20 has been substituted by Gly using oligonucleotide-directed mutagenesis [9].

Chemical compound and disease context of TUFM

• The role of helix alpha2 was studied by pre-steady-state kinetic experiments using Escherichia coli EF-Tu mutants where either Gly(83), Gly(94), or both were replaced with alanine [10].
• It is known that mutations of a conserved histidine residue in the switch II region of the factor, His84 in Escherichia coli EF-Tu, impair GTP hydrolysis [11].
• Complexes of the antibiotic, Phe-tRNA(Phe), the guanosine triphosphate analog GDPNP, and mesophilic (Escherichia coli), as well as thermophilic (Thermus thermophilus) EF-Tu were isolated [12].
• The conformation change of Thermus thermophilus tRNA(1Ile) upon complex formation with T. thermophilus elongation factor Tu (EF-Tu) was studied by analysis of the circular dichroism (CD) bands at 315 nm (due to the 2-thioribothymidine residue in the T-loop) and at 295 nm (due to the core structure of tRNA) [13].
• GTP complex at the active site of EF-Tu from Bacillus stearothermophilus has been investigated using thiophosphate analogs of GTP to inhibit the kirromycin-induced GTPase reaction at 60 mM NH4Cl [14].

Biological context of TUFM

• The TUFM gene is located on chromosome 16p11.2, with a putative pseudogene or variant (TUFML) located very close to the centromere of chromosome 17 [15].
• Chromosomal locations of three human nuclear genes (RPSM12, TUFM, and AFG3L1) specifying putative components of the mitochondrial gene expression apparatus [15].
• Based on these results, we suggest that SmpB structurally mimics the anticodon arm of tRNA and elicits GTP hydrolysis of EF-Tu upon tmRNA accommodation in the A site of the ribosome [16].
• The point mutation Gly94Ala in the switch 2 region of EF-Tu abolished the delay in P(i) release, suggesting that P(i) release is controlled by the mobility of the switch 2 region with Gly94 acting as a pivot [17].
• The selective similarities and differences of their binding sites and the induced EF-Tu conformations make understand how nature can affect the activities of a complex regulatory enzyme by means of low-molecular compounds, and have proposed a suitable approach for drug design [18].

Anatomical context of TUFM

• The human mitochondrial elongation factor Tu (EF-Tu) is nuclear-encoded and functions in the translational apparatus of mitochondria [19].
• Whereas low amounts of P43 are expressed in the spleen, skeletal muscle and pancreas, P43 is abundantly produced in the liver and in other tissues such as the kidney, heart and brain which have levels of oxidative metabolism [20].
• We also observed differential accumulation of proteins involved in expression of plastid-encoded proteins (e.g., EF-Tu, EF-G, and mRNA binding proteins) and thylakoid formation (VIPP1), whereas others were equally distributed [21].
• The steady-state levels of EFTs and EFTu in patient fibroblasts were reduced by 75% and 60%, respectively, and the amounts of assembled complexes I, IV, and V were reduced by 35%-91% compared with the amounts in controls [22].
• Partial sequences of the genes for plastid EF-Tu proteins (1,080-1,089 bp) were determined for three algae that contain chlorophyll b, namely, Gymnochlora stellata (Chlorarachniophyceae), Bryopsis maxima (Ulvophyceae), and Pyramimonas disomata (Prasinophyceae) [23].

Associations of TUFM with chemical compounds

• Although entry of the charged transfer messenger RNA (tmRNA) into the ribosome proceeded in the absence of elongation factor (EF-Tu) and in the presence of EF-Tu and the antibiotic kirromycin, evidence was found for the involvement of EF-Tu in trans-translation initiation [16].
• The polyalanine synthesis system attained by using a tmRNA variant consisting of only the tRNA-like domain revealed that it was completely dependent on the presence of SmpB and greatly enhanced by EF-Tu and EF-G [16].
• In both complexes, tetracycline makes significant interactions with the GTPase active site of EF-Tu [24].
• EFTs functions as a guanine nucleotide exchange factor for EFTu, another translation elongation factor that brings aminoacylated transfer RNAs to the ribosomal A site as a ternary complex with guanosine triphosphate [22].
• The trypsin-cleaved EF-Tu still can bind GDP and EF-Ts and can function in Qbeta replicase, but it no longer spontaneously renatures following denaturation in urea [25].

Other interactions of TUFM

• Extensive homologies were found in almost all cases and in the order S12 greater than EF-Tu greater than EF-G greater than S7; the largest homologies were generally found between the cyanobacterial proteins and the corresponding chloroplast gene products [26].
• The predicted amino acid sequence shows high similarity to other EF-Tu protein sequences from ox, yeast, and bacteria, and also shows limited similarity to human cystolic elongation factor 1 alpha [19].
• The str operon includes the structural genes rpsL (ribosomal protein S12), rpsG (ribosomal protein S7), fus (translation elongation factor EF-G) and tuf (translation elongation factor EF-Tu) [26].

Analytical, diagnostic and therapeutic context of TUFM

• The protein synthesis elongation factor EF-Tu was the first G-protein whose nucleotide binding domain was solved structurally by X-ray crystallography to yield a structural definition of the GDP-bound form, but a still increasing number of new structures of G-proteins are appearing in the literature, in both GDP and GTP bound forms [27].
• Isoelectric focusing separates 4 proteins from P43 during two dimensional electrophoresis, but only one of them is phosphorylated by A 23187 [28].
• The presence of EF-Tu at the surface of La1 was confirmed by analysis of purified outer surface protein extract by immunoblotting experiments, by electron microscopy, and by enzyme-linked immunosorbent assays of live bacteria [29].
• Western blot (immunoblot) analysis using both purified EF-Tu and EF-Tu domains confirmed that the unknown protein was EF-Tu [30].
• In consequence, we have used the anti-EF-Tu MAb 900 to design both a dot blot assay and an enzyme-linked immunosorbent assay [30].

References