title: A new type of protein lysine methyltransferase trimethylates Lys-79 of elongation factor 1A.
abstract: The elongation factors of Saccharomyces cerevisiae are extensively methylated, containing a total of ten methyllysine residues. Elongation factor methyltransferases (Efm1, Efm2, Efm3, and Efm4) catalyze at least four of these modifications. Here we report the identification of a new type of protein lysine methyltransferase, Efm5 (Ygr001c), which was initially classified as N6-adenine DNA methyltransferase-like. Efm5 is required for trimethylation of Lys-79 on EF1A. We directly show the loss of this modification in efm5Δ strains by both mass spectrometry and amino acid analysis. Close homologs of Efm5 are found in vertebrates, invertebrates, and plants, although some fungal species apparently lack this enzyme. This suggests possible unique functions of this modification in S. cerevisiae and higher eukaryotes. The misannotation of Efm5 was due to the presence of a DPPF sequence in post-Motif II, typically associated with DNA methylation. Further analysis of this motif and others like it demonstrates a potential consensus sequence for N-methyltransferases.
authors.affiliation: Department of Chemistry and Biochemistry and the Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Dzialo
authors.affiliation: Department of Chemistry and Biochemistry and the Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA.
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Travaglini
authors.affiliation: Department of Chemistry and Biochemistry and the Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Shen
authors.affiliation: Department of Chemistry and Biochemistry and the Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA; Department of Biological Chemistry and UCLA/DOE Institute for Genomics and Proteomics, UCLA, Los Angeles, CA 90095, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Loo
authors.affiliation: Department of Chemistry and Biochemistry and the Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA. Electronic address: clarke@chem.ucla.edu.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Clarke
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019295:Computational Biology; D019143:Evolution, Molecular; D017353:Gene Deletion; D005838:Genotype; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry*; D008239:Lysine / Q000031:analogs & derivatives / Q000737:chemistry*; D013058:Mass Spectrometry; D020648:Peptide Elongation Factor 1 / Q000737:chemistry*; D011499:Protein Processing, Post-Translational; D012436:S-Adenosylmethionine / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry
chemical_list: D020648:Peptide Elongation Factor 1; D029701:Saccharomyces cerevisiae Proteins; C003712:trimethyllysine; D012436:S-Adenosylmethionine; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine
keywords: Elongation factor; Methyltransferase; Posttranslational modification; Protein lysine methylation; S-adenosylmethionine (AdoMet)