title: The METTL20 Homologue from Agrobacterium tumefaciens Is a Dual Specificity Protein-lysine Methyltransferase That Targets Ribosomal Protein L7/L12 and the β Subunit of Electron Transfer Flavoprotein (ETFβ).
abstract: Human METTL20 is a mitochondrial, lysine-specific methyltransferase that methylates the β-subunit of electron transfer flavoprotein (ETFβ). Interestingly, putative METTL20 orthologues are found in a subset of α-proteobacteria, including Agrobacterium tumefaciens Using an activity-based approach, we identified in bacterial extracts two substrates of recombinant METTL20 from A. tumefaciens (AtMETTL20), namely ETFβ and the ribosomal protein RpL7/L12. We show that AtMETTL20, analogous to the human enzyme, methylates ETFβ on Lys-193 and Lys-196 both in vitro and in vivo ETF plays a key role in mediating electron transfer from various dehydrogenases, and we found that its electron transferring ability was diminished by AtMETTL20-mediated methylation of ETFβ. Somewhat surprisingly, AtMETTL20 also catalyzed monomethylation of RpL7/L12 on Lys-86, a common modification also found in many bacteria that lack METTL20. Thus, we here identify AtMETTL20 as the first enzyme catalyzing RpL7/L12 methylation. In summary, here we have identified and characterized a novel bacterial lysine-specific methyltransferase with unprecedented dual substrate specificity within the seven β-strand class of lysine-specific methyltransferases, as it targets two apparently unrelated substrates, ETFβ and RpL7/L12. Moreover, the present work establishes METTL20-mediated methylation of ETFβ as the first lysine methylation event occurring in both bacteria and humans.
authors.affiliation: From the Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo 0316, Norway.
authors.forename: Jędrzej
authors.initials: J
authors.lastname: Małecki
authors.affiliation: From the Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo 0316, Norway.
authors.forename: Helge-André
authors.initials: HA
authors.lastname: Dahl
authors.affiliation: From the Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo 0316, Norway.
authors.forename: Anders
authors.initials: A
authors.lastname: Moen
authors.affiliation: From the Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo 0316, Norway.
authors.forename: Erna
authors.initials: E
authors.lastname: Davydova
authors.affiliation: From the Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo 0316, Norway pal.falnes@ibv.uio.no.
authors.forename: Pål Ø
authors.initials: PØ
authors.lastname: Falnes
mesh_terms: D016960:Agrobacterium tumefaciens / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D044927:Electron-Transferring Flavoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000235:genetics / Q000378:metabolism*; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D044927:Electron-Transferring Flavoproteins; D007506:Iron-Sulfur Proteins; C053634:RPL7 protein, human; D012269:Ribosomal Proteins; D000587:Oxidoreductases Acting on CH-NH Group Donors; C023120:electron-transferring-flavoprotein dehydrogenase; C000594659:ETFBKMT protein, human; D008780:Methyltransferases
keywords: bacteria; energy metabolism; enzyme; post-translational modification (PTM); protein methylation; protein synthesis; ribosome