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Molecular basis for histone N-terminal methylation by NRMT1.

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Wu R, Yue Y, Zheng X, Li H
OpenAccess logo Genes Dev 29 2337-42 (2015)
Cited: 19 times
EuropePMC logo PMID: 26543159

Abstract

NRMT1 is an N-terminal methyltransferase that methylates histone CENP-A as well as nonhistone substrates. Here, we report the crystal structure of human NRMT1 bound to CENP-A peptide at 1.3 Å. NRMT1 adopts a core methyltransferase fold that resembles DOT1L and PRMT but not SET domain family histone methyltransferases. Key substrate recognition and catalytic residues were identified by mutagenesis studies. Histone peptide profiling revealed that human NRMT1 is highly selective to human CENP-A and fruit fly H2B, which share a common "Xaa-Pro-Lys/Arg" motif. These results, along with a 1.5 Å costructure of human NRMT1 bound to the fruit fly H2B peptide, underscore the importance of the NRMT1 recognition motif.

Reviews - 5cve mentioned but not cited (2)

  1. Chemical Biology of Protein N-Terminal Methyltransferases. Huang R. Chembiochem 20 976-984 (2019)
  2. Unlocking the mysteries of alpha-N-terminal methylation and its diverse regulatory functions. Chen P, Huang R, Hazbun TR. J Biol Chem 299 104843 (2023)

Articles - 5cve mentioned but not cited (1)

  1. Molecular basis for histone N-terminal methylation by NRMT1. Wu R, Yue Y, Zheng X, Li H. Genes Dev 29 2337-2342 (2015)


Reviews citing this publication (2)

  1. The upstreams and downstreams of H3K79 methylation by DOT1L. Vlaming H, van Leeuwen F. Chromosoma 125 593-605 (2016)
  2. Histone N-alpha terminal modifications: genome regulation at the tip of the tail. Demetriadou C, Koufaris C, Kirmizis A. Epigenetics Chromatin 13 29 (2020)

Articles citing this publication (14)

  1. α-amino trimethylation of CENP-A by NRMT is required for full recruitment of the centromere. Sathyan KM, Fachinetti D, Foltz DR. Nat Commun 8 14678 (2017)
  2. Design and characterization of PROTAC degraders specific to protein N-terminal methyltransferase 1. Zhou Q, Wu W, Jia K, Qi G, Sun XS, Li P. Eur J Med Chem 244 114830 (2022)
  3. Select human cancer mutants of NRMT1 alter its catalytic activity and decrease N-terminal trimethylation. Shields KM, Tooley JG, Petkowski JJ, Wilkey DW, Garbett NC, Merchant ML, Cheng A, Schaner Tooley CE. Protein Sci. 26 1639-1652 (2017)
  4. An Improved Top-Down Mass Spectrometry Characterization of Chlamydomonas reinhardtii Histones and Their Post-translational Modifications. Rommelfanger SR, Zhou M, Shaghasi H, Tzeng SC, Evans BS, Paša-Tolić L, Umen JG, Pesavento JJ. J Am Soc Mass Spectrom 32 1671-1688 (2021)
  5. Opposing regulation of the Nα-trimethylase METTL11A by its family members METTL11B and METTL13. Parker HV, Schaner Tooley CE. J Biol Chem 299 104588 (2023)
  6. An asparagine/glycine switch governs product specificity of human N-terminal methyltransferase NTMT2. Dong C, Dong G, Li L, Zhu L, Tempel W, Liu Y, Huang R, Min J. Commun Biol 1 183 (2018)
  7. Probing the Plasticity in the Active Site of Protein N-terminal Methyltransferase 1 Using Bisubstrate Analogues. Chen D, Dong C, Dong G, Srinivasan K, Min J, Noinaj N, Huang R. J Med Chem 63 8419-8431 (2020)
  8. The ribosome: A hot spot for the identification of new types of protein methyltransferases. Clarke SG. J. Biol. Chem. 293 10438-10446 (2018)
  9. Chemoproteomic Study Uncovers HemK2/KMT9 As a New Target for NTMT1 Bisubstrate Inhibitors. Chen D, Meng Y, Yu D, Noinaj N, Cheng X, Huang R. ACS Chem Biol 16 1234-1242 (2021)
  10. Discovery of Bisubstrate Inhibitors for Protein N-Terminal Methyltransferase 1. Chen D, Dong G, Noinaj N, Huang R. J. Med. Chem. 62 3773-3779 (2019)
  11. In vivo methylation of OLA1 revealed by activity-based target profiling of NTMT1. Jia K, Huang G, Wu W, Shrestha R, Wu B, Xiong Y, Li P. Chem Sci 10 8094-8099 (2019)
  12. Prolyl isomerization of the CENP-A N-terminus regulates centromeric integrity in fission yeast. Tan HL, Lim KK, Yang Q, Fan JS, Sayed AMM, Low LS, Ren B, Lim TK, Lin Q, Mok YK, Liou YC, Chen ES. Nucleic Acids Res. 46 1167-1179 (2018)
  13. Selective Peptidomimetic Inhibitors of NTMT1/2: Rational Design, Synthesis, Characterization, and Crystallographic Studies. Mackie BD, Chen D, Dong G, Dong C, Parker H, Schaner Tooley CE, Noinaj N, Min J, Huang R. J Med Chem 63 9512-9522 (2020)
  14. The N-terminal methyltransferase homologs NRMT1 and NRMT2 exhibit novel regulation of activity through heterotrimer formation. Faughn JD, Dean WL, Schaner Tooley CE. Protein Sci. 27 1585-1599 (2018)


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