Crystal Structure of Thermus thermophilus tRNA m1A58 Methyltransferase and Biophysical Characterization of Its Interaction with tRNA

Barraud, Pierre; Golinelli‐Pimpaneau, Béatrice; Atmanène, Cédric; Sanglier, Sarah; Dorsselaer, Alain Van; Droogmans, Louis; Dardel, Frédéric; Tisné, Carine

doi:10.1016/j.jmb.2008.01.041

Cited by 46 publications

(94 citation statements)

References 62 publications

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“…These facts suggest that the RNA recognition mechanism of RNA modification enzymes may have changed during molecular evolution process, even though the enzymes bring about the same modification(s) at the same position(s) in RNA. In another case of single-and multisite specific enzymes, eubacterial TrmI modifies only A58 in the T-loop of tRNA (56,57), whereas archaeal TrmI modifies both A57 and A58 (22). The RNA recognition mechanisms of eubacterial and archaeal TrmI may differ from each other, although both enzymes share structural relationships (57,58).…”

Section: Discussionmentioning

confidence: 99%

“…In another case of single-and multisite specific enzymes, eubacterial TrmI modifies only A58 in the T-loop of tRNA (56,57), whereas archaeal TrmI modifies both A57 and A58 (22). The RNA recognition mechanisms of eubacterial and archaeal TrmI may differ from each other, although both enzymes share structural relationships (57,58). In fact, it has been recently reported that the P. abyssi (archaeal) TrmI requires the A59 sequence for A58 methylation in tRNA, whereas Thermus thermophilus (eubacterial) TrmI does not require the A59 (58).…”

Section: Discussionmentioning

confidence: 99%

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Substrate tRNA Recognition Mechanism of a Multisite-specific tRNA Methyltransferase, Aquifex aeolicus Trm1, Based on the X-ray Crystal Structure

Awai

Ochi

Ihsanawati

et al. 2011

Journal of Biological Chemistry

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Archaeal and eukaryotic tRNA (N 2 ,N 2 -guanine)-dimethyltransferase (Trm1) produces N 2 ,N 2 -dimethylguanine at position 26 in tRNA. In contrast, Trm1 from Aquifex aeolicus, a hyper-thermophilic eubacterium, modifies G27 as well as G26. Here, a gel mobility shift assay revealed that the T-arm in tRNA is the binding site of A. aeolicus Trm1. To address the multisite specificity, we performed an x-ray crystal structure study. The overall structure of A. aeolicus Trm1 is similar to that of archaeal Trm1, although there is a zinc-cysteine cluster in the C-terminal domain of A. aeolicus Trm1. The N-terminal domain is a typical catalytic domain of S-adenosyl-L-methionine-dependent methyltransferases. On the basis of the crystal structure and amino acid sequence alignment, we prepared 30 mutant Trm1 proteins. These mutant proteins clarified residues important for S-adenosyl-L-methionine binding and enabled us to propose a hypothetical reaction mechanism. Furthermore, the tRNA-binding site was also elucidated by methyl transfer assay and gel mobility shift assay. The electrostatic potential surface models of A. aeolicus and archaeal Trm1 proteins demonstrated that the distribution of positive charges differs between the two proteins. We constructed a tRNA-docking model, in which the T-arm structure was placed onto the large area of positive charge, which is the expected tRNA-binding site, of A. aeolicus Trm1. In this model, the target G26 base can be placed near the catalytic pocket; however, the nucleotide at position 27 gains closer access to the pocket. Thus, this docking model introduces a rational explanation of the multisite specificity of A. aeolicus Trm1.Methylation is one of the most common chemical modifications that occurs in a broad range of biomolecules, including nucleic acids, proteins, lipids, and small compounds. It is implicated in a variety of cellular processes, such as translation, transcription, processing of RNA, epigenetics, development, carcinogenesis, neurotransmission, cellular transport, infection, and bacterial host defense. Among the RNA species, methylated nucleotides appear in most noncoding RNAs, constituting more than half of the post-transcriptional modifications identified so far. In particular, tRNA contains abundant methylated nucleotides, which stabilize the L-shaped tRNA structure and improve their molecular recognition (1-3).Among the methylated nucleotides in tRNA, N 2 ,N 2

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Substrate tRNA Recognition Mechanism of a Multisite-specific tRNA Methyltransferase, Aquifex aeolicus Trm1, Based on the X-ray Crystal Structure

Awai

Ochi

Ihsanawati

et al. 2011

Journal of Biological Chemistry

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“…For both of these complexes, it appears that the eukaryotic non-catalytic subunit has taken the place of one of the catalytic subunits of the bacterial homodimer, [35][36][37] perhaps to increase the substrate repertoire of the enzyme. 38,39 Tad2-Tad3, the A 34 deaminase Conversion of the wobble residue A 34 to I 34 (inosine) is thought to occur on the majority of tRNA species that encode an A 34 residue in bacteria and eukaryotes, but is not known to occur in archaea, which lack tRNA genes encoding A 34 .…”

Section: Heterodimers By Duplication and Divergencementioning

confidence: 99%

“…35,65 By contrast, m 1 A 58 modification of bacterial and archaeal tRNA is formed by only TrmI (the homolog of Trm61), based on the occurrence of only one Trm61 homolog and no obvious Trm6 homolog in bacterial and archaeal species, 66,68,69 and the activity of the purified Thermus thermophilus, M. tuberculosis, and Pyrococcus abyssi proteins. [68][69][70] Based on electrospray ionization mass spectrometry of the native complex, Tt TrmI is a homotetramer, 37 and it is also likely that the M. tuberculosis protein is homotetrameric, based on gel filtration analysis. 70 One of the major functions of Trm6 in the Trm6-Trm61 complex appears to be tRNA binding.…”

Section: Heterodimers By Duplication and Divergencementioning

confidence: 99%

“…Thus, S. cerevisiae and S. pombe mutants lacking Cm 32 and Gm 34, and S. pombe mutants lacking Gm 34 , have a severe growth defect due to reduced function of tRNA Phe , whereas S. cerevisiae or S. pombe mutants lacking only Cm 32 are healthy. [9][10][11] Furthermore, Cm 32 and Gm 34 on tRNA Phe are also important for the formation of wybutosine (yW 37 ) from m 1 G 37 in S. cerevisiae and S. pombe 10,11 (Fig. 2).…”

Section: Acquisition Of 2 Different Unrelated Subunits By Eukaryotes mentioning

confidence: 99%

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Two-subunit enzymes involved in eukaryotic post-transcriptional tRNA modification

Guy

Phizicky²

2014

RNA Biology

102

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The Design of RNA Binders: Targeting the HIV Replication Cycle as a Case Study

et al. 2014

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The human immunodeficiency virus 1 (HIV-1) replication cycle is finely tuned with many important steps involving RNA-RNA or protein-RNA interactions, all of them being potential targets for the development of new antiviral compounds. This cycle can also be considered as a good benchmark for the evaluation of early-stage strategies aiming at designing drugs that bind to RNA, with the possibility to correlate in vitro activities with antiviral properties. In this review, we highlight different approaches developed to interfere with four important steps of the HIV-1 replication cycle: the early stage of reverse transcription, the transactivation of viral transcription, the nuclear export of partially spliced transcripts and the dimerization step.

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Crystal Structure of Thermus thermophilus tRNA m1A58 Methyltransferase and Biophysical Characterization of Its Interaction with tRNA

Cited by 46 publications

References 62 publications

Substrate tRNA Recognition Mechanism of a Multisite-specific tRNA Methyltransferase, Aquifex aeolicus Trm1, Based on the X-ray Crystal Structure

Substrate tRNA Recognition Mechanism of a Multisite-specific tRNA Methyltransferase, Aquifex aeolicus Trm1, Based on the X-ray Crystal Structure

Two-subunit enzymes involved in eukaryotic post-transcriptional tRNA modification

The Design of RNA Binders: Targeting the HIV Replication Cycle as a Case Study

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