PMID:26929405

Citation	'Małecki, J, Dahl, HA, Moen, A, Davydova, E and Falnes, PØ (2016) The METTL20 Homologue from Agrobacterium tumefaciens Is a Dual-Specificity Protein Lysine Methyltransferase that Targets Ribosomal Protein L7/L12 and the Beta Subunit of Electron Transfer Flavoprotein (ETFβ). J. Biol. Chem. '
Abstract	Human METTL20 is a mitochondrial, lysine (K) specific methyltransferase (KMT) 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 found also in many bacteria that lack METTL20. Thus, we here identify AtMETTL20 as the first enzyme catalyzing RpL7/L12 methylation. In summary, we have here identified and characterized a novel bacterial KMT with unprecedented dual substrate specificity within the seven β-strand class of lysine-specific MTases, 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.
Links	PubMed Online version:10.1074/jbc.M115.709261
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
AGRFC:A9CHJ5		GO:0006479: protein methylation	ECO:0000314:		P		Figures 1, 2, 3, & 5 provide evidence of this enzyme activity.	complete
AGRFC:A9CHJ5		GO:0008168: methyltransferase activity	ECO:0000314:		F		Figures 1, 2, 3, and 5 provide evidence of this enzyme activity.	complete
AGRFC:A9CHJ5		GO:0008276: protein methyltransferase activity	ECO:0000314:		F		Figures 1, 2, 3, and 5 provide evidence of this enzymatic activity.	complete
AGRFC:A9CHJ5		GO:0016740: transferase activity	ECO:0000314:		F		Figures 1, 2, 3, and 5 provide evidence of this enzymatic activity.	complete

References

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