M-phase phosphoprotein 8 (MPP8) harbors an N-terminal chromodomain and a 
C-terminal ankyrin repeat domain. MPP8, via its chromodomain, binds histone H3 
peptide tri- or di-methylated at lysine 9 (H3K9me3/H3K9me2) in submicromolar 
affinity. We determined the crystal structure of MPP8 chromodomain in complex 
with H3K9me3 peptide. MPP8 interacts with at least six histone H3 residues from 
glutamine 5 to serine 10, enabling its ability to distinguish 
lysine-9-containing peptide (QTARKS) from that of lysine 27 (KAARKS), both 
sharing the ARKS sequence. A partial hydrophobic cage with three aromatic 
residues (Phe59, Trp80 and Tyr83) and one aspartate (Asp87) encloses the 
methylated lysine 9. MPP8 has been reported to be phosphorylated in vivo, 
including the cage residue Tyr83 and the succeeding Thr84 and Ser85. Modeling a 
phosphate group onto the side-chain hydroxyl oxygen of Tyr83 suggests that the 
negatively charged phosphate group could enhance the binding of positively 
charged methyl-lysine or create a regulatory signal by allowing or inhibiting 
binding of other protein(s).