The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes
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The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes. / Davydova, Erna; Shimazu, Tadahiro; Schuhmacher, Maren Kirstin; Jakobsson, Magnus E.; Willemen, Hanneke L.D.M.; Liu, Tongri; Moen, Anders; Ho, Angela Y.Y.; Małecki, Jędrzej; Schroer, Lisa; Pinto, Rita; Suzuki, Takehiro; Grønsberg, Ida A.; Sohtome, Yoshihiro; Akakabe, Mai; Weirich, Sara; Kikuchi, Masaki; Olsen, Jesper V.; Dohmae, Naoshi; Umehara, Takashi; Sodeoka, Mikiko; Siino, Valentina; McDonough, Michael A.; Eijkelkamp, Niels; Schofield, Christopher J.; Jeltsch, Albert; Shinkai, Yoichi; Falnes, Pål.
I: Nature Communications, Bind 12, 891, 2021.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes
AU - Davydova, Erna
AU - Shimazu, Tadahiro
AU - Schuhmacher, Maren Kirstin
AU - Jakobsson, Magnus E.
AU - Willemen, Hanneke L.D.M.
AU - Liu, Tongri
AU - Moen, Anders
AU - Ho, Angela Y.Y.
AU - Małecki, Jędrzej
AU - Schroer, Lisa
AU - Pinto, Rita
AU - Suzuki, Takehiro
AU - Grønsberg, Ida A.
AU - Sohtome, Yoshihiro
AU - Akakabe, Mai
AU - Weirich, Sara
AU - Kikuchi, Masaki
AU - Olsen, Jesper V.
AU - Dohmae, Naoshi
AU - Umehara, Takashi
AU - Sodeoka, Mikiko
AU - Siino, Valentina
AU - McDonough, Michael A.
AU - Eijkelkamp, Niels
AU - Schofield, Christopher J.
AU - Jeltsch, Albert
AU - Shinkai, Yoichi
AU - Falnes, Pål
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-020-20670-7
DO - 10.1038/s41467-020-20670-7
M3 - Journal article
C2 - 33563959
AN - SCOPUS:85100703102
VL - 12
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 891
ER -
ID: 258840952