Fig. 5: MD simulation analysis of the mechanism of DNMT3A activation.
From: Structural insight into hierarchical DNMT3A autoinhibition and its dysregulation in disease
a Close-up view of the structural overlay between the DNMT3A2-DNMT3L complex and the DNMT3AMTase-DNMT3LML-CpG DNA complex (PDB 5YX2), highlighting that the competition between the PWWP-ADD-TRD interaction and the TRD-DNA interaction. The TRD loop residue R836 interacts with ADD residues D529-D531 in the DNMT3A2-DNMT3L complex but CpG guanine (G1) in the DNA-bound form. The cytosine analogue used for structure determination, Zebularine, is labeled as Z0. The hydrogen bond between R836 and G1 is shown as a dashed line. b The RMSF values obtained for the ADD-MTase region in the structural model of the intact DNMT3A2-DNMT3L complex (3APWWP-ADD-MTase), the apo-DNMT3AADD-MTase-DNMT3L (3AADD-MTase), and the DNMT3AADD-MTase-DNMT3L-H3K4me0 complex (3AADD-MTase-H3). Data are mean ± s.d. (n = 3 independent runs). The mean RMSF values are shown as solid lines. The RMSF values within 1 s.d. are shown in shade. c Sausage view of the RMSF values of the 3APWWP-ADD-MTase, 3AADD-MTase, and 3AADD-MTase-H3, with the conformational transition of the TRD loop indicated by red arrow and the H3K4me0 peptide shown in sphere representation. Source data are provided as a Source Data file.
