SNAP-annotated 5mC-DNA-protein interactions: PDB entry 4x9j

PDB-id

4x9j; DSSR-derived features in text and JSON formats; DNAproDB

Class

transcription regulator-DNA

Method

X-ray (1.412 Å)

Summary

Egr-1 with doubly methylated DNA

Reference

Zandarashvili L, White MA, Esadze A, Iwahara J (2015): "Structural impact of complete CpG methylation within target DNA on specific complex formation of the inducible transcription factor Egr-1." Febs Lett., 589, 1748-1753. doi: 10.1016/j.febslet.2015.05.022.

Abstract

The inducible transcription factor Egr-1 binds specifically to 9-bp target sequences containing two CpG sites that can potentially be methylated at four cytosine bases. Although it appears that complete CpG methylation would make an unfavorable steric clash in the previous crystal structures of the complexes with unmethylated or partially methylated DNA, our affinity data suggest that DNA recognition by Egr-1 is insensitive to CpG methylation. We have determined, at a 1.4-Å resolution, the crystal structure of the Egr-1 zinc-finger complex with completely methylated target DNA. Structural comparison of the three different methylation states reveals why Egr-1 can recognize the target sequences regardless of CpG methylation.

• 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.