Extended Data Figure 2: Crystal structure of ADD–CD–C^DNMT3L in autoinhibitory form.

a, b, Two different views of the 2F_observed − F_calculated maps for C^DNMT3L (a) and CD (b) domains in the ADD–CD–C^DNMT3L structure. The maps were calculated at 3.82 Å and contoured at 1.5σ. Only main-chains are shown for simplicity. c, The 2F_observed − F_calculated maps for the ADD domain after refinement of the CD–C^DNMT3L complex (top) and after refinement of the ADD–CD–C^DNMT3L complex (bottom). The maps were calculated at 3.82 Å and contoured at 0.8σ. Main-chains from most residues, including residues 526–533 involved in the interaction with CD domain, fit well into the electron density. Some loop regions were not well covered by electron density, which is consistent with a high B factor (Extended Data Fig. 8a) of the ADD domain in the complex structure, supporting the dynamic feature of the ADD domain for regulating enzymatic activity of DNMT3A. d, Zn-anomalous difference map contoured at 3.5σ shows the positions of zinc cations in the ADD domain. e, Gel filtration profiles for standard proteins and the ADD–CD–C^DNMT3L complex. The peak position corresponds to the dimer of ADD–CD–C^DNMT3L with a molecular mass of about 140 kDa. f, Dimer formation of the ADD–CD–C^DNMT3L complex in crystals. The dimer of ADD–CD–C^DNMT3L complexes is mediated by CD–CD interaction in a two-fold crystallographic symmetry. Given the difficulty in tracing the conformation of the side chain in 3.82 Å resolution structure, we have not discussed the specific hydrogen bond or hydrophobic interaction within ADD–CD–C^DNMT3L. Residues 832–846 of DNMT3A were not built in the model because they lacked electron density, which may have resulted from their flexibility in crystals.