Methylation of proteins involved in translation

Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA.
Molecular Microbiology (Impact Factor: 4.42). 09/2007; 65(3):590-606. DOI: 10.1111/j.1365-2958.2007.05831.x
Source: PubMed


Methylation is one of the most common protein modifications. Many different prokaryotic and eukaryotic proteins are methylated, including proteins involved in translation, including ribosomal proteins (RPs) and translation factors (TFs). Positions of the methylated residues in six Escherichia coli RPs and two Saccharomyces cerevisiae RPs have been determined. At least two RPs, L3 and L12, are methylated in both organisms. Both prokaryotic and eukaryotic elongation TFs (EF1A) are methylated at lysine residues, while both release factors are methylated at glutamine residues. The enzymes catalysing methylation reactions, protein methyltransferases (MTases), generally use S-adenosylmethionine as the methyl donor to add one to three methyl groups that, in case of arginine, can be asymetrically positioned. The biological significance of RP and TF methylation is poorly understood, and deletions of the MTase genes usually do not cause major phenotypes. Apparently methylation modulates intra- or intermolecular interactions of the target proteins or affects their affinity for RNA, and, thus, influences various cell processes, including transcriptional regulation, RNA processing, ribosome assembly, translation accuracy, protein nuclear trafficking and metabolism, and cellular signalling. Differential methylation of specific RPs and TFs in a number of organisms at different physiological states indicates that this modification may play a regulatory role.

Download full-text


Available from: Bogdan Polevoda, Sep 30, 2015
29 Reads
  • Source
    • "Deletion of genes coding for protein methyltransferases involved in the modification of RPs and translation factors usu - ally do not cause major phenotypes and , in most cases , the functional role of methylation is not known ( Polevoda and Sherman 2007 , Clarke 2013 ) . Thus , a defect in RPL11 methyla - tion in bacteria is not accompanied by any dysfunction of the ribosomal machinery ( Vanet et al . "
    [Show abstract] [Hide abstract]
    ABSTRACT: Methylation of ribosomal proteins has long been described in prokaryotes and eukaryotes but our knowledge about the enzymes responsible for these modifications in plants is scarce. The bacterial protein methyltransferase PrmA catalyzes the trimethylation of ribosomal protein L11 (RPL11) at three distinct sites. The role of these modifications is still unknown. Here, we show that PrmA from Arabidopsis thaliana (AtPrmA) is dually-targeted to chloroplasts and mitochondria. Mass spectrometry and enzymatic assays indicated that the enzyme methylates RPL11 in plasto- and mitoribosomes in vivo. We determined that the Arabidopsis and Escherichia coli PrmA enzymes share similar product specificity, making trimethylated residues, but, despite evolutionary relationship, display a difference in substrate site specificity. Contrarily to the bacterial enzyme that trimethylates the ε-amino group of two lysine residues and the N-terminal α-amino group, AtPrmA methylates only one lysine in the MAFCK(D/E)(F/Y)NA motif of plastidial and mitochondrial RPL11. The plant enzyme possibly methylates the N-terminus of plastidial RPL11, whereas mitochondrial RPL11 is N-α-acetylated by an unknown acetyltransferase. Last, we found that an Arabidopsis prma-null mutant is viable in standard environmental conditions and no molecular defect could be associated with a lack of RPL11 methylation in leaf chloroplasts or mitochondria. However, the conservation of PrmA during the evolution of photosynthetic eukaryotes together with the location of methylated residues at the binding site of translation factors to ribosomes suggests that RPL11 methylation in plant organelles could be involved, in combination with other post-translational modifications, in optimizing ribosome function. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For Permissions, please e-mail:
    Plant and Cell Physiology 06/2015; 56(9). DOI:10.1093/pcp/pcv098 · 4.93 Impact Factor
  • Source
    • "Irrespective of copious publications in this field, studies have been extensively focused on the N-methylation on Lys or Arg residue [2–4,7–13]. Because the introduction of methyl groups within a protein usually has little effect in terms of analytical properties [2], challenges are remarkable for a global analysis of the methylated protein. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Unlabelled: Protein methylation catalyzed by SAM-dependent methyltransferase represents a major PTM involved in many important biological processes. Because methylation can occur on nitrogen, oxygen and sulfur centers and multiple methylation states exist on the nitrogen centers, methylproteome remains poorly documented. Here we present the methylation by isotope labeled SAM (MILS) strategy for a highly-confident analysis of the methylproteome of the yeast Saccharomyces cerevisiae based on the online multidimensional μHPLC/MS/MS technology. We identified 43 methylated proteins, containing 68 methylation events associated with 64 methylation sites. More than 90% of these methylation events were previously unannotated in Uniprot database. Our results indicated, 1) over 2.6% of identified S. cerevisiae proteins are methylated, 2) the amino acid residue preference of protein methylation follows the order Lys≫Arg>Asp>Asn≈Gln≈His>Glu>Cys, and 3) the methylation state on nitrogen center is largely exclusive. As our dataset covers various types of methylation centers, it provides rich information about yeast methylproteome and should significantly contribute to the field of protein methylation. Biological significance: In this paper, we presented the methylation by isotope labeled SAM (MILS) strategy for a highly-confident analysis of the methylproteome of the yeast S. cerevisiae and collected a comprehensive list of proteins methylated on a set of distinct residues (K, R, N, E, D, Q, H, C). Our study provided useful information about the amino acid residue preference and methylation state distributions on nitrogen centers of protein methylation in S. cerevisiae.
    Journal of Proteomics 08/2014; 114. DOI:10.1016/j.jprot.2014.07.032 · 3.89 Impact Factor
  • Source
    • "This allows unequivocal enzyme-substrate relationships to be built, for incorporation into methylproteome networks [5]. Elongation factors 1a and 2 are known to be methylated in eukaryotes [7] [8] [21]. In particular, we previously reported that S. cerevisiae elongation factor 2 (EF2), which catalyses the translocation step of translation elongation, is trimethylated at lysine 509 and dimethylated at lysine 613 [22]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Here we describe the discovery of S. cerevisiae protein YJR129Cp as a new eukaryotic seven-beta-strand lysine methyltransferase. An immunoblotting screen of 21 putative methyltransferases showed a loss in the methylation of elongation factor 2 (EF2) on knockout of YJR129C. Mass spectrometric analysis of EF2 tryptic peptides localized this loss of methylation to lysine 509, in peptide LVEGLKR. In vitro methylation, using recombinant methyltransferases and purified EF2, validated YJR129Cp as responsible for methylation of lysine 509 and Efm2p as responsible for methylation at lysine 613. Contextualised on previously described protein structures, both sites of methylation were found at the interaction interface between EF2 and the 40S ribosomal subunit. In line with the recently discovered Efm1 and Efm2 we propose that YJR129C be named elongation factor methyltransferase 3 (Efm3). The human homolog of Efm3 is likely to be the putative methyltransferase FAM86A, according to sequence homology and multiple lines of literature evidence.
    Biochemical and Biophysical Research Communications 07/2014; 451(2). DOI:10.1016/j.bbrc.2014.07.110 · 2.30 Impact Factor
Show more