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排序方式: 共有1344条查询结果,搜索用时 15 毫秒
1.
Nevena Cvetesic Mirna Bilus Ita Gruic-Sovulj 《The Journal of biological chemistry》2015,290(22):13981-13991
Aminoacyl-tRNA synthetases catalyze ATP-dependent covalent coupling of cognate amino acids and tRNAs for ribosomal protein synthesis. Escherichia coli isoleucyl-tRNA synthetase (IleRS) exploits both the tRNA-dependent pre- and post-transfer editing pathways to minimize errors in translation. However, the molecular mechanisms by which tRNAIle organizes the synthetic site to enhance pre-transfer editing, an idiosyncratic feature of IleRS, remains elusive. Here we show that tRNAIle affects both the synthetic and editing reactions localized within the IleRS synthetic site. In a complex with cognate tRNA, IleRS exhibits a 10-fold faster aminoacyl-AMP hydrolysis and a 10-fold drop in amino acid affinity relative to the free enzyme. Remarkably, the specificity against non-cognate valine was not improved by the presence of tRNA in either of these processes. Instead, amino acid specificity is determined by the protein component per se, whereas the tRNA promotes catalytic performance of the synthetic site, bringing about less error-prone and kinetically optimized isoleucyl-tRNAIle synthesis under cellular conditions. Finally, the extent to which tRNAIle modulates activation and pre-transfer editing is independent of the intactness of its 3′-end. This finding decouples aminoacylation and pre-transfer editing within the IleRS synthetic site and further demonstrates that the A76 hydroxyl groups participate in post-transfer editing only. The data are consistent with a model whereby the 3′-end of the tRNA remains free to sample different positions within the IleRS·tRNA complex, whereas the fine-tuning of the synthetic site is attained via conformational rearrangement of the enzyme through the interactions with the remaining parts of the tRNA body. 相似文献
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The speed and accuracy of protein synthesis are fundamental parameters for understanding the fitness of living cells, the quality control of translation, and the evolution of ribosomes. In this study, we analyse the speed and accuracy of the decoding step under conditions reproducing the high speed of translation in vivo. We show that error frequency is close to 10−3, consistent with the values measured in vivo. Selectivity is predominantly due to the differences in kcat values for cognate and near-cognate reactions, whereas the intrinsic affinity differences are not used for tRNA discrimination. Thus, the ribosome seems to be optimized towards high speed of translation at the cost of fidelity. Competition with near- and non-cognate ternary complexes reduces the rate of GTP hydrolysis in the cognate ternary complex, but does not appreciably affect the rate-limiting tRNA accommodation step. The GTP hydrolysis step is crucial for the optimization of both the speed and accuracy, which explains the necessity for the trade-off between the two fundamental parameters of translation. 相似文献
4.
V.N. Ksenzenko T.P. Kamynina S.I. Kazantsev M.G. Shlyapnikov V.M. Kryukov A.A. Bayev 《Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression》1982,697(2):235-242
One EcoRI-generated fragment (440 basepairs) and two EcoRI/HindIII fragments (220 and 960 basepairs) from the deletion region of T5 phage have been inserted into the phage λ XIII and the plasmid pBR322 as vectors. Recombinant DNA molecules were studied by hybridization with in vivo 32P-labeled T5 4–5 S RNAs on nitrocellulose filters. Two-dimensional polyacrylamide gel electrophoretic fractionation and fingerprint analysis of the RNAs eluted from the filters were carried out to identify RNAs coded by cloned fragments. For the accurate localization of the genes for these RNAs, RNA-DNA hybrids were treated with T1 and pancreatic RNAases, and the eluted RNA fragments stable against RNAase action were electrophoresed. It was shown that the EcoRI1440 fragment contains the gene for tRNA 10 (tRNAAsp), the EcoRI/HindIII1220 fragment contains the gene for RNA III (107 bases) and parts of the genes for RNA I (107 bases) and tRNA 12 (tRNAHis), and the EcoRI/HindIII1960 fragment contains only a part of the gene for tRNA 9 (tRNAGln). The arrangement of these genes on the physical map of T5 phage was as follows: -tRNAGln-tRNAHis-RNA III-RNA I-…-tRNAAsp. 相似文献
5.
Michael W. Hart Maria Byrne Michael J. Smith 《Evolution; international journal of organic evolution》1997,51(6):1848-1861
We analyzed phylogenetic relationships among 12 nominal species of starfish in the genera Patiriella and Asterina (Order Valvatida, Family Asterinidae), based on complete sequences for a mitochondrial protein coding gene (cytochrome oxidase subunit I) and five mitochondrial transfer RNA genes (alanine, leucine, asparagine, glutamine, and proline) (1923 bp total). The resulting phylogeny was used to test a series of hypotheses about the evolution of life-history traits. (1) A complex, feeding, planktonic larva is probably ancestral for these starfish, but this is not the most parsimonious reconstruction of ancestral larval states. (2) The feeding larval form was lost at least four times among these species, and three of these losses occurred among members of a single clade. (3) Small adult size evolved before both cases of hermaphroditism and viviparous brooding, but viviparity was not always preceded by an intermediate form of external brooding. (4) An ordered transformation series from feeding planktonic development to viviparous brooding has been predicted for starfish, but we could not find an example of this transformation series. (5) Viviparity evolved recently (< 2 Mya). (6) Both species selection and transformation of lineages may have contributed to the accumulation of species with nonfeeding development among these starfish. (7) Neither Asterina nor Patiriella are monophyletic genera. Larval forms and life-history traits of these starfish have evolved freely under no obvious constraints, contrary to the widely assumed evolutionary conservatism of early development. 相似文献
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In order to clarify the mechanisms of selenocysteine incorporation into glutathione peroxidase, some evidence to show the in vitro conversion of phosphoseryl-tRNA to selenocysteyl-tRNA is reported. [3H]Phosphoseryl-tRNA was incubated in a reaction mixture composed of SeO2, glutathione and NADPH in the presence of selenium-transferase partially purified. Analyses of amino acids on the product tRNA showed that a part (4%) of [3H]phosphoseryl-tRNA was changed to [3H]selenocysteyl-tRNA. The conversion from seryl-tRNAsu or major seryl-tRNAIGA was not found. Selenium-transferase was essential for the conversion. [3H]Selenocysteine, liberated from the tRNA, was modified with iodoacetic acid. The product was confirmed to be carboxymethyl-selenocysteine by two-dimensional TLC. Selenocysteyl-tRNAsu should be used to synthesize glutathione peroxidase by co-translational mechanisms. 相似文献
8.
A silver stain for the detection of nanogram amounts of tRNA following two-dimensional electrophoresis 总被引:6,自引:0,他引:6
G L Igloi 《Analytical biochemistry》1983,134(1):184-188
Three ultrasensitive protein silver-staining methods have been compared with respect to the detection of tRNA in polyacrylamide gels. The method of Sammons (D. W. Sammons, L.D. Adams, and E.E. Nishizawa (1981) Electrophoresis 2, 135-141) has been shown to have remarkable sensitivity, with a detection limit of 0.3 ng tRNA/mm2, allowing the two-dimensional fractionation of submicrogram amounts of bulk tRNA. The application of this technique to developmental and differentiation problems and other areas where the amounts of nonradioactive tRNA available are limited is anticipated. 相似文献
9.
Medha Raina Adil Moghal Amanda Kano Mathew Jerums Paul D. Schnier Shun Luo Rohini Deshpande Pavel V. Bondarenko Henry Lin Michael Ibba 《The Journal of biological chemistry》2014,289(25):17780-17790
Quality control operates at different steps in translation to limit errors to approximately one mistranslated codon per 10,000 codons during mRNA-directed protein synthesis. Recent studies have suggested that error rates may actually vary considerably during translation under different growth conditions. Here we examined the misincorporation of Phe at Tyr codons during synthesis of a recombinant antibody produced in tyrosine-limited Chinese hamster ovary (CHO) cells. Tyr to Phe replacements were previously found to occur throughout the antibody at a rate of up to 0.7% irrespective of the identity or context of the Tyr codon translated. Despite this comparatively high mistranslation rate, no significant change in cellular viability was observed. Monitoring of Phe and Tyr levels revealed that changes in error rates correlated with changes in amino acid pools, suggesting that mischarging of tRNATyr with noncognate Phe by tyrosyl-tRNA synthetase was responsible for mistranslation. Steady-state kinetic analyses of CHO cytoplasmic tyrosyl-tRNA synthetase revealed a 25-fold lower specificity for Tyr over Phe as compared with previously characterized bacterial enzymes, consistent with the observed increase in translation error rates during tyrosine limitation. Functional comparisons of mammalian and bacterial tyrosyl-tRNA synthetase revealed key differences at residues responsible for amino acid recognition, highlighting differences in evolutionary constraints for translation quality control. 相似文献
10.
《Journal of molecular biology》2021,433(15):167046
The ribosomal stalk protein plays a crucial role in functional interactions with translational GTPase factors. It has been shown that the archaeal stalk aP1 binds to both GDP- and GTP-bound conformations of aEF1A through its C-terminal region in two different modes. To obtain an insight into how the aP1•aEF1A binding mode changes during the process of nucleotide exchange from GDP to GTP on aEF1A, we have analyzed structural changes in aEF1A upon binding of the nucleotide exchange factor aEF1B. The isolated archaeal aEF1B has nucleotide exchange ability in the presence of aa-tRNA but not deacylated tRNA, and increases activity of polyphenylalanine synthesis 4-fold. The aEF1B mutation, R90A, results in loss of its original nucleotide exchange activity but retains a remarkable ability to enhance polyphenylalanine synthesis. These results suggest an additional functional role for aEF1B other than in nucleotide exchange. The crystal structure of the aEF1A•aEF1B complex, resolved at 2.0 Å resolution, shows marked rotational movement of domain 1 of aEF1A compared to the structure of aEF1A•GDP•aP1, and this conformational change results in disruption of the original aP1 binding site between domains 1 and 3 of aEF1A. The loss of aP1 binding to the aEF1A•aEF1B complex was confirmed by native gel analysis. The results suggest that aEF1B plays a role in switching off the interaction between aP1 and aEF1A•GDP, as well as in nucleotide exchange, and promote translation elongation. 相似文献