The extended B-strand conformation of the peptide forming a continuous B-sheet with the protein, is one of the two key elements of the peptide binding groove that is conserved among all Cbx proteins.

The second conserved element of the peptide binding groove, is a binding pocket for the Ala-25 residue in the peptide substrate, ALA25 is shown in red and in ball and stick model.

A recognition groove, with Asp 51 and Arg 53 as its residues, is important for peptide binding selectivity in Cbx2. Asp 51 and Arg 53 are shown in ball and stick model and in yellow and orangered, respectively.

The primary reason for the difference between human HP1 and Pc chromodomains lies in their electrostatic surfaces. HP1 homologs have a large electronegative peptide binding surface, while dPc homologs have much more hydrophobic surfaces, resulting in having lower affinity for the basic histone peptides. Hydrophobic and polar residues are shown in magenta and white. H3K27me3 peptide is shown in cyan.

Hydrophobic clasp, is formed by Val-11 and Leu-50 in dPc chromodomain homologs. Ala-24 of the H3K27me3 peptide interacts with this hydrophobic clasp in all four Pc-class complex structures. Leu 50, Ala 24 and Val 11 are colored coral, cyan and yellow, respectively.

Crystal Structure of chromodomain of CBX2 in complex with UNC3866, s a potent and cellularly active inhibitor of Cbx2 chromodomain. UNC3866 is displayed in red.