Site-specific lysine methylation of histones by SET domains is a hallmark for epigenetic control of gene transcription in eukaryotic organisms. Here we report that a SET domain protein from Paramecium bursaria chlorella virus can specifically di-methylate Lys27 in histone H3, a modification implicated in gene silencing. The solution structure of the viral SET domain reveals a butterfly-shaped head-to-head symmetric dimer different from other known protein methyltransferases. Each subunit consists of a Greek-key antiparallel β-barrel and a three-stranded open-faced sandwich that mediates the dimer interface. Cofactor S-adenosyl-L-methionine (SAM) binds at the opening of the β-barrel, and amino acids C-terminal to Lys27 in H3 and in the flexible C-terminal tail of the enzyme confer the specificity of this viral histone methyltransferase.
ASJC Scopus subject areas
- Structural Biology