Disease relevance of TSFM

• Both the mature and precursor forms of bovine liver EF-Tsmt have been expressed in E. coli as histidine-tagged proteins [1].
• The effects of either trastuzumab, CIK cells alone, or CD3xHer2/neu bispecific antibody redirected CIK cells was determined using a SCID/hu model of EFTs and serial, noninvasive bioluminescent imaging [2].
• Thus, efts have a variety of behaviors that reduce the risk of dehydration associated with climate change [3].
• Between October 1989 and November 1998, 822 patients with a clinical diagnosis of GERD (based on symptoms and endoscopic findings) were referred for EFTs [4].
• METHODS: The study was performed on a series of 27 EFTs (osseous Ewing's sarcoma, 18 cases; extraosseous Ewing's sarcoma, 2; peripheral neuroepithelioma, 4; Askin Rosai tumors, 3) [5].

High impact information on TSFM

• The most important effects are: (i) a strong reduction of the intrinsic GTPase activity, (ii) a remarkable enhancement of the association and dissociation rates of EF-TuGly20-GDP, mimicking the effect of elongation factor Ts (EF-Ts) and (iii) the inability of ribosomes to influence the intrinsic GTPase of EF-Tu uncoupled from poly(Phe) synthesis [6].
• As with the latter, poly(Phe) synthesis by EF-TuGly20 is inhibited by the antibiotic kirromycin, but differs remarkably in that it is largely independent of the presence of EF-Ts [6].
• 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 [7].
• 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 [7].
• These phenotypes and the translation defect were rescued by retroviral expression of either EFTs or EFTu [7].

Biological context of TSFM

• Assignment of the mitochondrial translation elongation factor Ts gene (TSFM) to human chromosome 12 bands q13-->q14 by in situ hybridization and with somatic cell hybrids [8].
• The deduced amino acid sequence of bovine liver EF-Tsmt is 338 residues in length and includes a 55-amino acid signal peptide and a mature protein of 283 residues [1].
• The results suggest that EF-Ts and kirromycin induce a similar conformational change in EF-Tu, thereby "opening" the guanine nucleotide binding site [9].
• Oscillation occurs during GTP hydrolysis and subsequent replacement of GDP by EF-Ts which is then displaced by GTP [10].
• The kinetics of the exchange reaction were found to be consistent with the formation of a ternary complex EF-Tu X GTP X EF-Ts [11].

Anatomical context of TSFM

• Northern analysis using a human multiple tissue blot indicates that EF-Tsmt is expressed in all tissues, with the highest levels of expression in skeletal muscle, liver, and kidney [1].
• Whereas EF-Ts is lacking in S. cerevisiae, both translation factors are found in S. pombe and H. sapiens mitochondria, consistent with the known similarity between fission yeast and human cell mitochondrial physiology [12].
• In this study we show that the inhibition of protein synthesis by MDL 62,879 in an Escherichia coli cell-free system was fully reversed by addition of stoichiometric amounts of EF-Tu but not by large excesses of EF-Ts, ribosomes, or aa-tRNA [13].
• Right upper limbs of 20 efts were examined at low magnification to establish carpal composition and organization [14].
• Delayed carpal ossification in Notophthalmus viridescens Efts: Relation to the progress of mesopodial completion in newt forelimb regenerates [14].

Associations of TSFM with chemical compounds

• Two of these polypeptides, protein synthesis elongation factors EF-Tu and EF-Ts, can be covalently crosslinked with dimethyl suberimidate to form a complex which lacks the ability to catalyze the known host functions catalyzed by the individual elongation factors [15].
• 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 [9].
• GDP is a competitive inhibitor of IDP exchange, a result predicted for the substituted enzyme mechanism but inconsistent with ternary complex mechanisms that involve an intermediate complex containing EF-Ts and both substrates [16].
• The effects of pulvomycin and EF-Ts can coexist and are simply additive, supporting the conclusion that these two ligands interact with different sites of EF-Tu [17].
• Steady-state and dynamic polarization measurements revealed limited local mobility for the tryptophan in the EF-Tu x GDP complex whereas formation of the EF-Tu x EF-Ts complex led to a dramatic increase in this local mobility [18].

Physical interactions of TSFM

• Asp83 has a conformation similar to the conformation of the corresponding residue in the EF-Tu/EF-Ts complex [19].

Regulatory relationships of TSFM

• In the wheat system, however, both EF-1b and EF-1b' had the EF-Ts-like activity to stimulate EF-1a-dependent binding of aminoacyl-tRNA to ribosomes [20].

Other interactions of TSFM

• EF-Tu/GDP is recycled by the guanine nucleotide exchange factor EF-Ts [12].
• Renaturation of rhodanese and GTP hydrolysis by EF-Tu are greatly enhanced by the guanine nucleotide exchange factor EF-Ts [10].
• In agreement with studies on EF-Ts and human EF-1beta, a functional mechanism for nucleotide exchange is proposed wherein Phe46 on an exposed loop acts as a lever to eject GDP from the associated elongation factor G-protein, aEF-1alpha. aEF-1beta was also found to bind calcium in the groove between helix alpha2 and strand beta4 [21].
• In the animal system, EF-1a and EF-1b correspond functionally to EF-Tu and EF-Ts, respectively [20].

Analytical, diagnostic and therapeutic context of TSFM

• When exposed to combined desiccation and predation risks, efts were less active than when exposed to either risk separately and avoided adult tissue extracts, but not eft extracts [3].
• Interactions of EF-Ts with EF-Tu at all steps of the elongation cycle were studied by limited trypsinolysis, gel-filtration, analytical centrifugation and fluorescence polarization techniques [22].
• Esophageal function tests (EFTs: esophageal manometry and 24-hr pH monitoring) are generally reserved for patients who have the most severe disease, including those being considered for surgery [4].
• We hypothesized that EFTs are more accurate than symptoms and endoscopy in the diagnosis of GERD [4].
• EFTs are characterized by specific chromosomal translocations that result in chimeric transcripts that can be detected with reverse transcriptase-polymerase chain reaction (RT-PCR) analysis [23].

References