Fig. 2: RD interface variation underpins distinct oligomerization behavior between DNMT3A and DNMT3B.
From: Structure-guided functional suppression of AML-associated DNMT3A hotspot mutations
a Structural overlay of the RD interfaces of DNMT3A and DNMT3B (PDB 8EIH), with residues involved in intermolecular interactions shown in stick representation. Hydrogen-bonding and electrostatic interactions are shown as red and black dashed lines, respectively. b Close-up view of DNMT3A-unique RD interface residues M674, R676, and H821, with the intermolecular sidechain distances between R676′ (prime symbol denotes residue from the symmetry-related subunit) and E820 labeled in unit of Å. c Close-up view of DNMT3B-unique RD interface residues T615, K617, and Y762, with the side-chain distances between K617′ and E761 from the symmetry-related subunit labeled in unit of Å. d Size-exclusion chromatography analysis of DNMT3A fragment comprised of the PWWP, ADD and MTase domains, WT, R882H, R882H/R676K, or R882H/R676K/M674T mutant. The elution volumes for molecular weight standards (thyroglobulin: 669 kDa, ferritin: 440 kDa, adolase: 158 kDa) are indicated by arrows. e Size-exclusion chromatography analysis of DNMT3B fragment comprised of the PWWP, ADD and MTase domains, WT or R823H mutant.
