A novel 3-methylhistidine modification of yeast ribosomal protein Rpl3 is dependent upon the YIL110W methyltransferase. Academic Article uri icon


  • We have shown that Rpl3, a protein of the large ribosomal subunit from baker's yeast (Saccharomyces cerevisiae), is stoichiometrically monomethylated at position 243, producing a 3-methylhistidine residue. This conclusion is supported by top-down and bottom-up mass spectrometry of Rpl3, as well as by biochemical analysis of Rpl3 radiolabeled in vivo with S-adenosyl-l-[methyl-(3)H]methionine. The results show that a +14-Da modification occurs within the GTKKLPRKTHRGLRKVAC sequence of Rpl3. Using high-resolution cation-exchange chromatography and thin layer chromatography, we demonstrate that neither lysine nor arginine residues are methylated and that a 3-methylhistidine residue is present. Analysis of 37 deletion strains of known and putative methyltransferases revealed that only the deletion of the YIL110W gene, encoding a seven β-strand methyltransferase, results in the loss of the +14-Da modification of Rpl3. We suggest that YIL110W encodes a protein histidine methyltransferase responsible for the modification of Rpl3 and potentially other yeast proteins, and now designate it Hpm1 (Histidine protein methyltransferase 1). Deletion of the YIL110W/HPM1 gene results in numerous phenotypes including some that may result from abnormal interactions between Rpl3 and the 25 S ribosomal RNA. This is the first report of a methylated histidine residue in yeast cells, and the first example of a gene required for protein histidine methylation in nature.

published proceedings

  • J Biol Chem

altmetric score

  • 3

author list (cited authors)

  • Webb, K. J., Zurita-Lopez, C. I., Al-Hadid, Q., Laganowsky, A., Young, B. D., Lipson, R. S., ... Clarke, S. G

citation count

  • 62

complete list of authors

  • Webb, Kristofor J||Zurita-Lopez, Cecilia I||Al-Hadid, Qais||Laganowsky, Arthur||Young, Brian D||Lipson, Rebecca S||Souda, Puneet||Faull, Kym F||Whitelegge, Julian P||Clarke, Steven G

publication date

  • September 2010