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. |