SNAP output for PDB entry 7l4n [SNAP web server]

PDB-id

7l4n; SNAP-derived features in text and JSON formats; DNAproDB

Class

DNA binding protein-DNA

Method

X-ray (2.247 Å)

Summary

Crystal structure of the drm2 (c397r)-ccg DNA complex

Reference

Fang J, Leichter SM, Jiang J, Biswal M, Lu J, Zhang ZM, Ren W, Zhai J, Cui Q, Zhong X, Song J (2021): "Substrate deformation regulates DRM2-mediated DNA methylation in plants." Sci Adv, 7. doi: 10.1126/sciadv.abd9224.

Abstract

DNA methylation is a major epigenetic mechanism critical for gene expression and genome stability. In plants, domains rearranged methyltransferase 2 (DRM2) preferentially mediates CHH (H = C, T, or A) methylation, a substrate specificity distinct from that of mammalian DNA methyltransferases. However, the underlying mechanism is unknown. Here, we report structure-function characterization of DRM2-mediated methylation. An arginine finger from the catalytic loop intercalates into the nontarget strand of DNA through the minor groove, inducing large DNA deformation that affects the substrate preference of DRM2. The target recognition domain stabilizes the enlarged major groove via shape complementarity rather than base-specific interactions, permitting substrate diversity. The engineered DRM2 C397R mutation introduces base-specific contacts with the +2-flanking guanine, thereby shifting the substrate specificity of DRM2 toward CHG DNA. Together, this study uncovers DNA deformation as a mechanism in regulating the specificity of DRM2 toward diverse CHH substrates and illustrates methylome complexity in plants.