Structural similarities in glutaminyl- and methionyl-tRNA synthetases suggest a common overall orientation of tRNA binding.

Perona, John J.; Rould, Mark A.; Steitz, Thomas A.; Risler, Jean‐Loup; Zelwer, C.; Brunie, Simone

doi:10.1073/pnas.88.7.2903

Cited by 66 publications

(45 citation statements)

References 34 publications

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“…The nonrotated distance is 3.84 Å. (25) and GluRS (residues 300-321) (26) enzymes, but is absent in TyrRS and TrpRS enzymes. Other studies indicate that the general orientation of the tRNA substrates on TyrRS and TrpRS is distinct from that in other class I systems (27).…”

Section: Resultsmentioning

confidence: 99%

The importance of tRNA backbone-mediated interactions with synthetase for aminoacylation

McClain

Schneider

Bhattacharya

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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We have identified six new aminoacylation determinants of Escherichia coli tRNA Gln in a genetic and biochemical analysis of suppressor tRNA. The new determinants occupy the interior of the acceptor stem, the inside corner of the L shape, and the anticodon loop of the molecule. They supplement the primary determinants located in the anticodon and acceptor end of tRNA Gln described previously. Remarkably, the three-dimensional structure of the complex between tRNA Gln and glutaminyl-tRNA synthetase shows that the enzyme interacts with the phosphate-sugar backbone but not the base of every new determinant. Moreover, a small protein motif interacts with five of these determinants, and it binds proximal to the sixth. The motif also interacts with the middle base of the anticodon and with the backbones of six other nucleotides. Our results emphasize that synthetase recognition of tRNA is more elaborate than amino acid side chains of the enzyme interacting with nucleotide bases of the tRNA. Recognition also includes synthetase interaction with tRNA backbone functionalities whose distinctive locations in three-dimensional space are exquisitely determined by the tRNA sequence.

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Section: Resultsmentioning

confidence: 99%

The importance of tRNA backbone-mediated interactions with synthetase for aminoacylation

McClain

Schneider

Bhattacharya

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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“…The domain connects the acceptor and anticodon binding domains of the tRNA synthetases and may provide a functional communication of anticodon recognition between the anticodon binding domain to the acceptor region binding domain and active site of the synthetases (32). Interestingly, even though a high degree of structural homology is found for the fold in the Gln-and Met-tRNA synthetases, no significant sequence similarity exists, although generally the C-terminal helix in the motif has a net negative charge despite its location adjacent to the highly negatively charged phosphate backbone of the tRNA (33). A similar pattern is found in the case of IF2, where there is no obvious sequence homology for the surface residues of the subdomain, but a net negative charge is found for the region corresponding to helix ␣3 of the subdomain in the great majority of bacterial sequences investigated.…”

Section: Discussionmentioning

confidence: 99%

A Conserved Structural Motif at the N Terminus of Bacterial Translation Initiation Factor IF2

Laursen

Mortensen

Sperling‐Petersen

et al. 2003

Journal of Biological Chemistry

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The 18-kDa Domain I from the N-terminal region of translation initiation factor IF2 from Escherichia coli was expressed, purified, and structurally characterized using multidimensional NMR methods. Residues 2-50 were found to form a compact subdomain containing three short ␤-strands and three ␣-helices, folded to form a ␤␣␣␤␤␣ motif with the three helices packed on the same side of a small twisted ␤-sheet. The hydrophobic amino acids in the core of the subdomain are conserved in a wide range of species, indicating that a similarly structured motif is present at the N terminus of IF2 in many of the bacteria. External to the compact 50-amino acid subdomain, residues 51-97 are less conserved and do not appear to form a regular structure, whereas residues 98 -157 form a helix containing a repetitive sequence of mostly hydrophilic amino acids. Nitrogen-15 relaxation rate measurements provide evidence that the first 50 residues form a well ordered subdomain, whereas other regions of Domain I are significantly more mobile. The compact subdomain at the N terminus of IF2 shows structural homology to the tRNA anticodon stem contact fold domains of the methionyl-tRNA and glutaminyl-tRNA synthetases, and a similar fold is also found in the B5 domain of the phenylalanine-tRNA synthetase. The results of the present work will provide guidance for the design of future experiments directed toward understanding the functional roles of this widely conserved structural domain within IF2.

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“…Extensive experiments have been carried out to establish the importance of several amino acid residues in MetRS and the nucleotides of tRNA in the recognition processes. For instance, the loop containing highly conserved residue Trp-461 plays a crucial role in the recognition of anticodon bases, as confirmed by affinity-labeling experiments (5), isolation of second site mutants (6), and docking studies of glutaminyl-tRNA on MetRS (7). Substitution of highly conserved residues Trp-461, Asn-452, or Arg-395 shows their involvement in the binding of MetRS to anticodon site of tRNA (8)(9)(10).…”

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confidence: 97%

A study of communication pathways in methionyl- tRNA synthetase by molecular dynamics simulations and structure network analysis

Ghosh

Vishveshwara

2007

Proc. Natl. Acad. Sci. U.S.A.

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288

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The enzymes of the family of tRNA synthetases perform their functions with high precision by synchronously recognizing the anticodon region and the aminoacylation region, which are separated by Ϸ70 Å in space. This precision in function is brought about by establishing good communication paths between the two regions. We have modeled the structure of the complex consisting of Escherichia coli methionyl-tRNA synthetase (MetRS), tRNA, and the activated methionine. Molecular dynamics simulations have been performed on the modeled structure to obtain the equilibrated structure of the complex and the cross-correlations between the residues in MetRS have been evaluated. Furthermore, the network analysis on these simulated structures has been carried out to elucidate the paths of communication between the activation site and the anticodon recognition site. This study has provided the detailed paths of communication, which are consistent with experimental results. Similar studies also have been carried out on the complexes (MetRS ؉ activated methonine) and (MetRS ؉ tRNA) along with ligand-free native enzyme. A comparison of the paths derived from the four simulations clearly has shown that the communication path is strongly correlated and unique to the enzyme complex, which is bound to both the tRNA and the activated methionine. The details of the method of our investigation and the biological implications of the results are presented in this article. The method developed here also could be used to investigate any protein system where the function takes place through longdistance communication.dynamic cross-correlations ͉ methionyl-AMP ͉ protein structure network ͉ shortest pathways of communication ͉ stacking A crucial step in the translation of the genetic code is the aminoacylation of tRNA, which involves the molecular recognition between the aminoacyl-tRNA synthetases (aaRS) and their cognate tRNA. Each synthetase consists of the catalytic domain and the anticodon domain that are separated by Ϸ70 Å. Each tRNA connects these two regions with its anticodon and the acceptor stems. The mechanism of differentiations between cognate and noncognate tRNAs depends on contacts of anticodon domain of synthetase and anticodon stem of tRNA. The efficiency of the selection mechanism controls the overall accuracy of protein synthesis (1, 2). Recognition of the protein (aaRS) and the tRNA is explained by using the induced-fit mechanism, which suggests conformational changes in protein, tRNA, or both, leading to the final bound complex (3). However, the details of communication between the anticodon region and the aminoacylation region are less understood.In all living cells, protein synthesis starts with methionine.

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Structural similarities in glutaminyl- and methionyl-tRNA synthetases suggest a common overall orientation of tRNA binding.

Cited by 66 publications

References 34 publications

The importance of tRNA backbone-mediated interactions with synthetase for aminoacylation

The importance of tRNA backbone-mediated interactions with synthetase for aminoacylation

A Conserved Structural Motif at the N Terminus of Bacterial Translation Initiation Factor IF2

A study of communication pathways in methionyl- tRNA synthetase by molecular dynamics simulations and structure network analysis

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