FIGURE 1.

DNMT3A homodimer interface. A, DNMT3A-DNMT3L heterotetramer based on the crystal structure (Protein Data Bank code 2QRV), showing the dimer and tetramer interface; the boxed region is enlarged below. B, the dimer interface is symmetrical; shown is a close-up of half the interface and all of the center interactions. Underlined residues were mutated in this study. The interface has many ionic interactions and a few aromatic residues. Residues are colored based upon their predicted energetic contribution to the dimer interface, in ΔΔG, compared with alanine as determined using the Rosetta interface alanine scanning module. Bright yellow residues provide the greatest contribution to the DNMT3A-DNMT3A interface. Boxed is the full dimer interface showing both symmetrical sides of the dimer interface.