The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes
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...
| Principais autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Journal article |
| Idioma: | English |
| Publicado em: |
Springer Nature
2021
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| _version_ | 1826274603592318976 |
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| author | 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, PØ |
| author_facet | 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, PØ |
| author_sort | Davydova, E |
| collection | OXFORD |
| description | 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.
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| first_indexed | 2024-03-06T22:45:57Z |
| format | Journal article |
| id | oxford-uuid:5d2edc4d-b490-4789-a8f9-e3a23c7392d4 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:45:57Z |
| publishDate | 2021 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:5d2edc4d-b490-4789-a8f9-e3a23c7392d42022-03-26T17:33:00ZThe methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5d2edc4d-b490-4789-a8f9-e3a23c7392d4EnglishSymplectic ElementsSpringer Nature2021Davydova, EShimazu, TSchuhmacher, MKJakobsson, MEWillemen, HLDMLiu, TMoen, AHo, AYYMałecki, JSchroer, LPinto, RSuzuki, TGrønsberg, IASohtome, YAkakabe, MWeirich, SKikuchi, MOlsen, JVDohmae, NUmehara, TSodeoka, MSiino, VMcDonough, MAEijkelkamp, NSchofield, CJJeltsch, AShinkai, YFalnes, PØPost-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. |
| spellingShingle | 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, PØ The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes |
| title | The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes |
| title_full | The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes |
| title_fullStr | The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes |
| title_full_unstemmed | The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes |
| title_short | The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes |
| title_sort | methyltransferase mettl9 mediates pervasive 1 methylhistidine modification in mammalian proteomes |
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