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

PDB-id

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

Class

transcription-DNA

Method

X-ray (0.99 Å)

Summary

Mouse zfp57 zinc fingers in complex with methylated DNA

Reference

Liu Y, Toh H, Sasaki H, Zhang X, Cheng X (2012): "An atomic model of Zfp57 recognition of CpG methylation within a specific DNA sequence." Genes Dev., 26, 2374-2379. doi: 10.1101/gad.202200.112.

Abstract

Zinc finger transcription factor Zfp57 recognizes the methylated CpG within the TGCCGC element. We determined the structure of the DNA-binding domain of Zfp57, consisting of two adjacent zinc fingers, in complex with fully methylated DNA at 1.0 Å resolution. The first zinc finger contacts the 5' half (TGC), and the second recognizes the 3' half (CGC) of the recognition sequence. Zfp57 recognizes the two 5-methylcytosines (5mCs) asymmetrically: One involves hydrophobic interactions with Arg178, which also interacts with the neighboring 3' guanine and forms a 5mC-Arg-G interaction, while the other involves a layer of ordered water molecules. Two point mutations in patients with transient neonatal diabetes abolish DNA-binding activity. Zfp57 has reduced binding affinity for unmodified DNA and the oxidative products of 5mC.

• 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.