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.

In: Nature Communications, Vol. 12, No. 1, 891, 2021.

Research output: Contribution to journalArticle

Harvard

Davydova, E, Shimazu, T, Schuhmacher, MK, Jakobsson, ME, Willemen, HLDM, Liu, T, Moen, A, Ho, AYY, Małecki, J, Schroer, L, Pinto, R, Suzuki, T, Grønsberg, IA, Sohtome, Y, Akakabe, M, Weirich, S, Kikuchi, M, Olsen, JV, Dohmae, N, Umehara, T, Sodeoka, M, Siino, V, McDonough, MA, Eijkelkamp, N, Schofield, CJ, Jeltsch, A, Shinkai, Y & Falnes, P 2021, 'The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes', Nature Communications, vol. 12, no. 1, 891. https://doi.org/10.1038/s41467-020-20670-7

APA

Davydova, E., Shimazu, T., Schuhmacher, M. K., Jakobsson, M. E., Willemen, H. L. D. M., Liu, T., Moen, A., Ho, A. Y. Y., Małecki, J., Schroer, L., Pinto, R., Suzuki, T., Grønsberg, I. A., Sohtome, Y., Akakabe, M., Weirich, S., Kikuchi, M., Olsen, J. V., Dohmae, N., ... Falnes, P. (2021). The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes. Nature Communications, 12(1), [891]. https://doi.org/10.1038/s41467-020-20670-7

CBE

Davydova E, Shimazu T, Schuhmacher MK, Jakobsson ME, Willemen HLDM, Liu T, Moen A, Ho AYY, Małecki J, Schroer L, Pinto R, Suzuki T, Grønsberg IA, Sohtome Y, Akakabe M, Weirich S, Kikuchi M, Olsen JV, Dohmae N, Umehara T, Sodeoka M, Siino V, McDonough MA, Eijkelkamp N, Schofield CJ, Jeltsch A, Shinkai Y, Falnes P. 2021. The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes. Nature Communications. 12(1):Article 891. https://doi.org/10.1038/s41467-020-20670-7

MLA

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Author

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. / The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes. In: Nature Communications. 2021 ; Vol. 12, No. 1.

RIS

TY - JOUR

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 - Article

C2 - 33563959

AN - SCOPUS:85100703102

VL - 12

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 891

ER -