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

Research output: Contribution to journalArticle


title = "The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes",
abstract = "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.",
author = "Erna Davydova and Tadahiro Shimazu and Schuhmacher, {Maren Kirstin} and Jakobsson, {Magnus E.} and Willemen, {Hanneke L.D.M.} and Tongri Liu and Anders Moen and Ho, {Angela Y.Y.} and J{\c e}drzej Ma{\l}ecki and Lisa Schroer and Rita Pinto and Takehiro Suzuki and Gr{\o}nsberg, {Ida A.} and Yoshihiro Sohtome and Mai Akakabe and Sara Weirich and Masaki Kikuchi and Olsen, {Jesper V.} and Naoshi Dohmae and Takashi Umehara and Mikiko Sodeoka and Valentina Siino and McDonough, {Michael A.} and Niels Eijkelkamp and Schofield, {Christopher J.} and Albert Jeltsch and Yoichi Shinkai and P{\aa}l Falnes",
year = "2021",
doi = "10.1038/s41467-020-20670-7",
language = "English",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",