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: 5.03). 09/2007; 65(3):590-606. DOI: 10.1111/j.1365-2958.2007.05831.x
Source: PubMed

ABSTRACT 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, Aug 14, 2015
  • 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: 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, 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.
    Journal of Proteomics 08/2014; 114. DOI:10.1016/j.jprot.2014.07.032 · 3.93 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 · 2.28 Impact Factor
  • Source
    • "The largest group of AdoMet-dependent methyltransferases methylates proteins, predominantly at the ε-amine group of lysine and ω-or δ-guanidine groups of arginine as well as on the C-terminal leucine and isoprenylated cysteine residues. Targets of AdoMet-dependent protein methyltransferases include histones, ribosomal proteins, transcription and translation factors, signal transduction proteins etc. [19] [20] [21] [22]. For instance, the SET domain protein lysine methyltransferase family, which makes up 27% of human methyltransferasome and 14% of yeast methyltransferasome, methylates predominantly histones at lysine residues [17] [23]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: S-adenosyl-L-methionine (AdoMet)-dependent methylation is central to the regulation of many biological processes: more than 50 AdoMet-dependent methyltransferases methylate a broad spectrum of cellular compounds including nucleic acids, proteins and lipids. Common to all AdoMet-dependent methyltransferase reactions is the release of the strong product inhibitor S-adenosyl-L-homocysteine (AdoHcy), as a by-product of the reaction. S-adenosyl-L-homocysteine hydrolase is the only eukaryotic enzyme capable of reversible AdoHcy hydrolysis to adenosine and homocysteine and, thus, relief from AdoHcy inhibition. Impaired S-adenosyl-L-homocysteine hydrolase activity in humans results in AdoHcy accumulation and severe pathological consequences. Hyperhomocysteinemia, which is characterized by elevated levels of homocysteine in blood, also exhibits a similar phenotype of AdoHcy accumulation due to the reversal of the direction of the S-adenosyl-L-homocysteine hydrolase reaction. Inhibition of S-adenosyl-L-homocysteine hydrolase is also linked to antiviral effects. In this review the advantages of yeast as an experimental system to understand pathologies associated with AdoHcy accumulation will be discussed.
    Biochimica et Biophysica Acta 09/2012; 1832(1). DOI:10.1016/j.bbadis.2012.09.007 · 4.66 Impact Factor
Show more