Extended Data Fig. 5: Structure analysis of DNMT3A2-3L bound to nucleosomes.
From: Mechanisms of DNMT3A–3L-mediated de novo DNA methylation on chromatin
a,b, Overall cryo-EM map fittings of NCP (a) and DNMT3A2-3L (b). Inlet, unsharpened density map fitting the distal DNMT3A2 ADD domain. c, Density map fittings of the distal DNMT3L CLD domain. DNMT3L C-ter “Switching Helix” was indicated by the arrow. d, Top: active (PDB ID 4U7T) and autoinhibitory (PDB ID 4U7P) forms of DNMT3A ADD-CD dimers. Bottom: Structure comparison of current nucleosome-bound DNMT3A2-3L with autoinhibitory form of DNMT3A ADD-CD dimer (PDB ID 4U7P). Only DNMT3A2 ADD-CD dimers were shown. e, Structure comparison of proximal DNMT3L with active form (left) and autoinhibitory form (right) of DNMT3A ADD-CD domains (PDB ID 4U7T and 4U7P). f, Interfaces of the DNMT3A (CD)-3L(CLD) in crystal structure (PDB ID 2QRV). DNMT3A CD can form a V-shaped, polar, homodimeric interface (3A-3A RD interface) while with DNMT3L CLD, DNMT3A CD can form a flat, non-polar, heterodimeric interface (3A-3L FF interface) due to lack of the TRD loops in DNMT3L. g, Density map of the CD-DNA interaction region generated in ChimeraX with contour level at 0.1 (left) and 0.005 (right). The expected flipped C base position in the active site was highlighted in red. h, Density maps of the two SAH ligands generated in ChimeraX and level at 0.05.
