Structural basis for the methylation site specificity of SET7/9

Jean François Couture, Evys Collazo, Glenn Hauk, Raymond C. Trievel

Research output: Contribution to journalArticlepeer-review

130 Scopus citations


Human SET7/9 is a protein lysine methyltransferase (PKMT) that methylates histone H3, the tumor suppressor p53 and the TBP-associated factor TAF10. To elucidate the determinants of its substrate specificity, we have solved the enzyme's structure bound to a TAF10 peptide and examined its ability to methylate histone H3, TAF10 and p53 substrates bearing either mutations or covalent modifications within their respective methylation sites. Collectively, our data reveal that SET7/9 recognizes a conserved K/R-S/T/A motif preceding the lysine substrate and has a propensity to bind aspartates and asparagines on the C-terminal side of the lysine target. We then used a sequence-based approach with this motif to identify novel substrates for this PKMT. Among the putative targets is TAF7, which is methylated at Lys5 by the enzyme in vitro. These results demonstrate the predictive value of the consensus motif in identifying novel substrates for SET7/9.

Original languageEnglish (US)
Pages (from-to)140-146
Number of pages7
JournalNature Structural and Molecular Biology
Issue number2
StatePublished - Feb 3 2006
Externally publishedYes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


Dive into the research topics of 'Structural basis for the methylation site specificity of SET7/9'. Together they form a unique fingerprint.

Cite this