SNAP-annotated 5mC-DNA-protein interactions: PDB entry 4m9e

PDB-id

4m9e; DSSR-derived features in text and JSON formats; DNAproDB

Class

transcription-DNA

Method

X-ray (1.851 Å)

Summary

Structure of klf4 zinc finger DNA binding domain in complex with methylated DNA

Reference

Liu Y, Olanrewaju YO, Zheng Y, Hashimoto H, Blumenthal RM, Zhang X, Cheng X (2014): "Structural basis for Klf4 recognition of methylated DNA." Nucleic Acids Res., 42, 4859-4867. doi: 10.1093/nar/gku134.

Abstract

Transcription factor Krüppel-like factor 4 (Klf4), one of the factors directing cellular reprogramming, recognizes the CpG dinucleotide (whether methylated or unmodified) within a specific G/C-rich sequence. The binding affinity of the mouse Klf4 DNA-binding domain for methylated DNA is only slightly stronger than that for an unmodified oligonucleotide. The structure of the C-terminal three Krüppel-like zinc fingers (ZnFs) of mouse Klf4, in complex with fully methylated DNA, was determined at 1.85 Å resolution. An arginine and a glutamate interact with the methyl group. By comparison with two other recently characterized structures of ZnF protein complexes with methylated DNA, we propose a common principle of recognition of methylated CpG by C2H2 ZnF proteins, which involves a spatially conserved Arg-Glu pair.

• 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.