SNAP-annotated 5mC-DNA-protein interactions: PDB entry 6a5n

PDB-id

6a5n; DSSR-derived features in text and JSON formats; DNAproDB

Class

gene regulation-DNA

Method

X-ray (2.4 Å)

Summary

Crystal structure of arabidopsis thaliana suvh6 in complex with methylated DNA

Reference

Li X, Harris CJ, Zhong Z, Chen W, Liu R, Jia B, Wang Z, Li S, Jacobsen SE, Du J (2018): "Mechanistic insights into plant SUVH family H3K9 methyltransferases and their binding to context-biased non-CG DNA methylation." Proc. Natl. Acad. Sci. U.S.A., 115, E8793-E8802. doi: 10.1073/pnas.1809841115.

Abstract

DNA methylation functions in gene silencing and the maintenance of genome integrity. In plants, non-CG DNA methylation is linked through a self-reinforcing loop with histone 3 lysine 9 dimethylation (H3K9me2). The plant-specific SUPPRESSOR OF VARIEGATION 3-9 HOMOLOG (SUVH) family H3K9 methyltransferases (MTases) bind to DNA methylation marks and catalyze H3K9 methylation. Here, we analyzed the structure and function of <i>Arabidopsis thaliana</i> SUVH6 to understand how this class of enzyme maintains methylation patterns in the genome. We reveal that SUVH6 has a distinct 5-methyl-dC (5mC) base-flipping mechanism involving a thumb loop element. Autoinhibition of H3 substrate entry is regulated by a SET domain loop, and a conformational transition in the post-SET domain upon cofactor binding may control catalysis. In vitro DNA binding and in vivo ChIP-seq data reveal that the different SUVH family H3K9 MTases have distinct DNA binding preferences, targeting H3K9 methylation to sites with different methylated DNA sequences, explaining the context biased non-CG DNA methylation in plants.

• The contacts include paired nucleotides (mostly a G in Watson-Crick G-C pairing) and amino-acids within a 4.5-Å distance cutoff to base atoms of 5mC.
• The structure is oriented in the base reference frame of 5mC, allowing for easy comparison and direct superimposition between entries.
• The black sphere (•) denotes the 5-methyl carbon atom in 5mC.