9MVY

Crystal structure of ZMET2 in complex with unmethylated CTG DNA and a histone H3Kc9me2 peptide

Summary for 9MVY

• Entry DOI: 10.2210/pdb9mvy/pdb
• Descriptor: DNA (cytosine-5)-methyltransferase 1, ssDNA, C49 ssDNA, ... (6 entities in total)
• Functional Keywords: methylation complex, epigenetics, and dna methyltransferase, transferase
• Biological source: Zea mays; More
• Total number of polymer chains: 10
• Total formula weight: 206801.74

Authors

Herle, G.,Fang, J.,Song, J. (deposition date: 2025-01-16, release date: 2025-05-21)

Primary citation

Herle, G.,Fang, J.,Song, J.
Structure of an unfavorable de novo DNA methylation complex of plant methyltransferase ZMET2.
J.Mol.Biol., :169186-169186, 2025

PubMed Abstract: DNA methylation is an important epigenetic mechanism that controls the assembly of heterochromatin and gene expression. In plants, DNA methylation occurs in both CG and non-CG contexts, with non-CG methylation showing notable substrate sequence dependence. The plant DNA methyltransferase CMT3 mediates maintenance of CHG (H = A, C, or T) DNA methylation, with a strong substrate preference for the hemimethylated CWG (W = A, T) motif. Yet, the underlying mechanism remains elusive. Here we present a crystal structure of ZMET2, the CMT3 ortholog from Zea mays (maize), in complex with a DNA substrate containing an unmethylated CTG motif and a histone peptide carrying a mimic of the histone H3K9me2 modification. Structural comparison of the ZMET2-CTG complex with the previously reported structure of ZMET2 bound to hemimethylated CAG DNA reveals similar but distinct protein-DNA interactions centered on the CWG motif, providing insight into the methylation state- and substrate sequence-specific ZMET2/CMT3-substrate interaction. Furthermore, our combined structural and biochemical analysis reveals a role for the +3-flanking base of the target cytosine in fine-tuning ZMET2-mediated DNA methylation and its functional interplay with the +1- and +2-flanking sites. Together, these results provide deep mechanistic insights into the substrate specificity of CMT3 DNA methyltransferases in plants.

PubMed: 40335018
DOI: 10.1016/j.jmb.2025.169186

Experimental method

X-RAY DIFFRACTION (2.71 Å)