Publications

• The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes.

  Davydova E., Shimazu T., Schuhmacher M.K., Jakobsson M.E., Willemen H.L.D.M., Liu T., Moen A., Ho A.Y.Y., Malecki J., Schroer L., Pinto R., Suzuki T., Groensberg I.A., Sohtome Y., Akakabe M., Weirich S., Kikuchi M., Olsen J.V., Dohmae N., Umehara T., Sodeoka M., Siino V., McDonough M.A., Eijkelkamp N., Schofield C.J., Jeltsch A., Shinkai Y., Falnes P.O.

  Post-translational methylation plays a crucial role in regulating and optimizing protein function. Protein histidine methylation, occurring as the two isomers 1- and 3-methylhistidine (1MH and 3MH), was first reported five decades ago, but remains largely unexplored. Here we report that METTL9 is ... >> More

  Post-translational methylation plays a crucial role in regulating and optimizing protein function. Protein histidine methylation, occurring as the two isomers 1- and 3-methylhistidine (1MH and 3MH), was first reported five decades ago, but remains largely unexplored. Here we report that METTL9 is a broad-specificity methyltransferase that mediates the formation of the majority of 1MH present in mouse and human proteomes. METTL9-catalyzed methylation requires a His-x-His (HxH) motif, where "x" is preferably a small amino acid, allowing METTL9 to methylate a number of HxH-containing proteins, including the immunomodulatory protein S100A9 and the NDUFB3 subunit of mitochondrial respiratory Complex I. Notably, METTL9-mediated methylation enhances respiration via Complex I, and the presence of 1MH in an HxH-containing peptide reduced its zinc binding affinity. Our results establish METTL9-mediated 1MH as a pervasive protein modification, thus setting the stage for further functional studies on protein histidine methylation. << Less

  Nat. Commun. 12:891-891(2021) [PubMed] [EuropePMC]