Molecular basis for histone N-terminal methylation by NRMT1

Genes Dev. 2015 Nov 15;29(22):2337-42. doi: 10.1101/gad.270926.115. Epub 2015 Nov 5.


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.

Keywords: CENP-A; N-terminal methylation; NRMT1; crystal structure; epigenetic regulation; histone modification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantigens / chemistry
  • Autoantigens / metabolism*
  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone / chemistry
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster
  • Escherichia coli / genetics
  • Histones / chemistry
  • Histones / metabolism
  • Methylation
  • Methyltransferases / genetics
  • Methyltransferases / metabolism*
  • Models, Molecular*
  • Mutagenesis
  • Protein Structure, Tertiary
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism


  • Autoantigens
  • CENPA protein, human
  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone
  • Drosophila Proteins
  • Histones
  • Recombinant Proteins
  • Methyltransferases
  • NTMT1 protein, human

Associated data

  • PDB/5CVD
  • PDB/5CVE