Human METTL20 is a mitochondrial lysine methyltransferase that targets the β subunit of electron transfer flavoprotein (ETFβ) and modulates its activity.

作者: Jędrzej Małecki , Angela Y. Y. Ho , Anders Moen , Helge-André Dahl , Pål Ø. Falnes

DOI: 10.1074/JBC.M114.614115

关键词: Protein targetingBiochemistryHistone methyltransferaseHistoneProtein methylationMethylationMethyltransferaseElectron-transferring flavoproteinLysineBiology

摘要: Proteins are frequently modified by post-translational methylation of lysine residues, catalyzed S-adenosylmethionine-dependent methyltransferases (KMTs). Lysine histone proteins has been extensively studied, but it recently become evident that non-histone is also abundant and important. The human methyltransferase METTL20 belongs to a group 10 established putative KMTs. We here found be associated with mitochondria determined recombinant methylated single protein in extracts from cells. Using an activity-based purification scheme, we identified the β-subunit mitochondrially localized electron transfer flavoprotein (ETFβ) as substrate METTL20. Furthermore, was specifically methylate two adjacent Lys(200) Lys(203), ETFβ both vitro Interestingly, residues partially overlap so-called "recognition loop" ETFβ, which shown mediate its interaction various dehydrogenases. Accordingly, METTL20-mediated reduced ability receive electrons medium chain acyl-CoA dehydrogenase glutaryl-CoA dehydrogenase. In conclusion, present study establishes first KMT suggests may regulate cellular metabolism through modulating between Based on previous naming similar enzymes, suggest renaming ETFβ-KMT.

参考文章(36)
M C McKean, J D Beckmann, F E Frerman, Subunit structure of electron transfer flavoprotein. Journal of Biological Chemistry. ,vol. 258, pp. 1866- 1870 ,(1983) , 10.1016/S0021-9258(18)33068-0
R R Ramsay, D J Steenkamp, M Husain, Reactions of electron-transfer flavoprotein and electron-transfer flavoprotein: ubiquinone oxidoreductase. Biochemical Journal. ,vol. 241, pp. 883- 892 ,(1987) , 10.1042/BJ2410883
Jing Huang, Shelley L Berger, The emerging field of dynamic lysine methylation of non-histone proteins Current Opinion in Genetics & Development. ,vol. 18, pp. 152- 158 ,(2008) , 10.1016/J.GDE.2008.01.012
Paul A. Del Rizzo, Raymond C. Trievel, Substrate and product specificities of SET domain methyltransferases Epigenetics. ,vol. 6, pp. 1059- 1067 ,(2011) , 10.4161/EPI.6.9.16069
Steven G. Clarke, Protein methylation at the surface and buried deep: thinking outside the histone box Trends in Biochemical Sciences. ,vol. 38, pp. 243- 252 ,(2013) , 10.1016/J.TIBS.2013.02.004
Qin Feng, Hengbin Wang, Huck Hui Ng, Hediye Erdjument-Bromage, Paul Tempst, Kevin Struhl, Yi Zhang, Methylation of H3-Lysine 79 Is Mediated by a New Family of HMTases without a SET Domain Current Biology. ,vol. 12, pp. 1052- 1058 ,(2002) , 10.1016/S0960-9822(02)00901-6
Roberta Magnani, Lynnette M.A. Dirk, Raymond C. Trievel, Robert L. Houtz, Calmodulin methyltransferase is an evolutionarily conserved enzyme that trimethylates Lys-115 in calmodulin Nature Communications. ,vol. 1, pp. 43- 43 ,(2010) , 10.1038/NCOMMS1044