Recognition of ribosomal protein L11 by the protein trimethyltransferase PrmA

DeMi̇rci̇, Hasan; Gregory, Steven T.; Dahĺberg, Albert E.; Jogl, G.

doi:10.1038/sj.emboj.7601508

Cited by 33 publications

(36 citation statements)

References 41 publications

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“…V17 is highly conserved in the aKMT proteins and corresponds to T107 in PrmA, as shown by sequence alignment. It may be involved in SAM binding, as has been reported for T107 in PrmA (16). Taken together, these data suggest an important role for the 6-HVPYVPTPE-14 motif in methyl transfer by aKMT.…”

Section: Fig 3 Inhibition Of the Cren7-methylating Activity Of The Ssupporting

confidence: 62%

“…The T/S conservation raises the possibility that the side chain hydroxyl group of the amino acid is directly involved in the catalysis of the methyltransfer reaction. In the T. thermophilus PrmA protein, whose C-terminal catalytic domain shows similarity to aKMT in amino acid sequence, the active site contains two key residues, H104 and T106 (16). The role of the T/S residue in aKMT may resemble that of T106.…”

Section: Discussionmentioning

confidence: 99%

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Identification and Characterization of a Highly Conserved Crenarchaeal Protein Lysine Methyltransferase with Broad Substrate Specificity

et al. 2012

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Protein lysine methylation occurs extensively in the Crenarchaeota, a major kingdom in the Archaea. However, the enzymes responsible for this type of posttranslational modification have not been found. Here we report the identification and characterization of the first crenarchaeal protein lysine methyltransferase, designated aKMT, from the hyperthermophilic crenarchaeon Sulfolobus islandicus. The enzyme was capable of transferring methyl groups to selected lysine residues in a substrate protein using S-adenosyl-L-methionine (SAM) as the methyl donor. aKMT, a non-SET domain protein, is highly conserved among crenarchaea, and distantly related homologs also exist in Bacteria and Eukarya. aKMT was active over a wide range of temperatures, from ϳ25 to 90°C, with an optimal temperature at ϳ60 to 70°C. Amino acid residues Y9 and T12 at the N terminus appear to be the key residues in the putative active site of aKMT, as indicated by sequence conservation and site-directed mutagenesis. Although aKMT was identified based on its methylating activity on Cren7, the crenarchaeal chromatin protein, it exhibited broad substrate specificity and was capable of methylating a number of recombinant Sulfolobus proteins overproduced in Escherichia coli. The finding of aKMT will help elucidate mechanisms underlining extensive protein lysine methylation and the functional significance of posttranslational protein methylation in crenarchaea.

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Section: Fig 3 Inhibition Of the Cren7-methylating Activity Of The Ssupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Identification and Characterization of a Highly Conserved Crenarchaeal Protein Lysine Methyltransferase with Broad Substrate Specificity

et al. 2012

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“…Nishimura et al (2007b) reported that mutation of Thr42 (Thr53 in T. thermophilus) to asparagine in this highly conserved loop gives rise to streptomycin resistance, suggesting that the identity of this threonine residue and structural flexibility of the loop region are important for function. Flexible active site loops have also been observed in ribosomal protein L11 methyltransferase PrmA (Demirci et al 2007(Demirci et al , 2008b and in the rRNA methyltransferase KsgA (Demirci et al 2009). …”

Section: Structural Comparison With Related Enzymesmentioning

confidence: 88%

Structural and functional studies of the Thermus thermophilus 16S rRNA methyltransferase RsmG

Gregory¹,

DeMi̇rci̇²,

Belardinelli³

et al. 2009

RNA

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The RsmG methyltransferase is responsible for N 7 methylation of G527 of 16S rRNA in bacteria. Here, we report the identification of the Thermus thermophilus rsmG gene, the isolation of rsmG mutants, and the solution of RsmG X-ray crystal structures at up to 1.5 Å resolution. Like their counterparts in other species, T. thermophilus rsmG mutants are weakly resistant to the aminoglycoside antibiotic streptomycin. Growth competition experiments indicate a physiological cost to loss of RsmG activity, consistent with the conservation of the modification site in the decoding region of the ribosome. In contrast to Escherichia coli RsmG, which has been reported to recognize only intact 30S subunits, T. thermophilus RsmG shows no in vitro methylation activity against native 30S subunits, only low activity with 30S subunits at low magnesium concentration, and maximum activity with deproteinized 16S rRNA. Cofactor-bound crystal structures of RsmG reveal a positively charged surface area remote from the active site that binds an adenosine monophosphate molecule. We conclude that an early assembly intermediate is the most likely candidate for the biological substrate of RsmG.

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“…It is not known whether PrmA can in fact catalyze the modification of all sites, or whether a PrmA-dependent reaction is required for the action of one or more distinct methyltransferases that modify the N-terminus and the lysine side chains. However, x-ray structures of the PrmA ortholog from Thermus thermophilus have been interpreted to suggest how this protein may be able to position its L11 substrate for multiple methylation reactions (72).…”

Section: Unusual Dual Protein Methyltransferases That May Recognize Bmentioning

confidence: 99%

The ribosome: A hot spot for the identification of new types of protein methyltransferases

Clarke¹

2018

Journal of Biological Chemistry

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Cellular physiology depends on the alteration of protein structures by covalent modification reactions. Using a combination of bioinformatic, genetic, biochemical, and mass spectrometric approaches, it has been possible to probe ribosomal proteins from the yeast Saccharomyces cerevisiae for posttranslationally methylated amino acid residues and for the enzymes that catalyze these modifications. These efforts have resulted in the identification and characterization of the first protein histidine methyltransferase, the first N-terminal protein methyltransferase, two unusual types of protein arginine methyltransferases, and a new type of cysteine methylation. Two of these enzymes may modify their substrates during ribosomal assembly because the final methylated histidine and arginine residues are buried deep within the ribosome with contacts only with RNA. Two of these modifications occur broadly in eukaryotes, including humans, while the others demonstrate a more limited phylogenetic range. Analysis of strains where the methyltransferase genes are deleted has given insight into the physiological roles of these modifications. These reactions described here add diversity to the modifications that generate the typical methylated lysine and arginine residues previously described in histones and other proteins. Regulation of biological function by protein methylation reactionsIt is more and more apparent just how much of biological function is dependent upon posttranslational modifications (1). The human genome encodes some 900 enzymes catalyzing just protein phosphorylation or ubiquitination (2,3). However, it is now clear that methyl groups can stand beside phosphate groups and ubiquitin as major players in controlling the physiological functions of proteins. We are beginning to understand how the much greater diversity of protein methylation reactions can give rise to a greater diversity of function (1,4-8). We are also learning the importance of crosstalk between protein and DNA methylation reactions (9) and among protein methylation, phosphorylation, acetylation, and ubiquitination reactions (10-12). Finally, we are discovering how alterations in protein methylation pathways can lead to human pathology, particularly in cancer (13-15).The collection of over sixty human protein arginine and lysine methyltransferases that leave histone "marks" recognized by reader proteins to guide gene expression are perhaps the poster children for the importance of protein methyltransferases (16-17). However, recent work has emphasized the importance of methylating non-histone substrates at these residues, particularly ribosomal proteins, translation factors, and transcription factors in a wide variety of organisms (7,8,15,18,19). Furthermore, the methylation of lysine and arginine residues represents just the tip of the iceberg in protein methylation -modifications have also been established at histidine, modified histidine (diphthamide), glutamate, glutamine, asparagine, Lisoaspartate, D-aspartate, cysteine, isoprenylcysteine, me...

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Recognition of ribosomal protein L11 by the protein trimethyltransferase PrmA

Cited by 33 publications

References 41 publications

Identification and Characterization of a Highly Conserved Crenarchaeal Protein Lysine Methyltransferase with Broad Substrate Specificity

Identification and Characterization of a Highly Conserved Crenarchaeal Protein Lysine Methyltransferase with Broad Substrate Specificity

Structural and functional studies of the Thermus thermophilus 16S rRNA methyltransferase RsmG

The ribosome: A hot spot for the identification of new types of protein methyltransferases

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