5mC interactions in PDB entry 5EGO auto-curated with SNAP

Last updated on 2019-09-30 by Xiang-Jun Lu <xiangjun@x3dna.org>. The block schematics were created with DSSR and rendered using PyMOL.

Summary information and primary citation [schematics · contacts · top · homepage · tutorial]

PDB-id

5EGO

Class

transcription

Method

X-ray (2.54 Å)

Summary

Hoxb13-meis1 heterodimer bound to methylated DNA
List of 2 5mC-amino acid contacts:

D.5CM33: hydrophobic-with-B.ILE262 is-WC-paired is-in-duplex [+]:AcG/cGT

E.5CM4: hydrophobic-with-B.VAL269 is-WC-paired is-in-duplex [-]:cGA/TcG

direct SNAP output · DNAproDB 2.0

Reference

Yin, Y., Morgunova, E., Jolma, A., Kaasinen, E., Sahu, B., Khund-Sayeed, S., Das, P.K., Kivioja, T., Dave, K., Zhong, F., Nitta, K.R., Taipale, M., Popov, A., Ginno, P.A., Domcke, S., Yan, J., Schubeler, D., Vinson, C., Taipale, J.: (2017) "Impact of cytosine methylation on DNA binding specificities of human transcription factors." Science, 356

Abstract

The majority of CpG dinucleotides in the human genome are methylated at cytosine bases. However, active gene regulatory elements are generally hypomethylated relative to their flanking regions, and the binding of some transcription factors (TFs) is diminished by methylation of their target sequences. By analysis of 542 human TFs with methylation-sensitive SELEX (systematic evolution of ligands by exponential enrichment), we found that there are also many TFs that prefer CpG-methylated sequences. Most of these are in the extended homeodomain family. Structural analysis showed that homeodomain specificity for methylcytosine depends on direct hydrophobic interactions with the methylcytosine 5-methyl group. This study provides a systematic examination of the effect of an epigenetic DNA modification on human TF binding specificity and reveals that many developmentally important proteins display preference for mCpG-containing sequences.

Base-block schematics in six views [summary · contacts · top · homepage · tutorial]

The 5-methylcytosine group (PDB ligand '5CM') is shown in space-filling model, with the methyl-carbon atom in black.
Watson-Crick base pairs are represented as long rectangular blocks with the minor-groove edge in black. Color code: A-T red, C-G yellow, G-C green, T-A blue.
Protein is shown as cartoon in purple. DNA backbones are shown ribbon, colored code by chain identifier.
The block schematics were created with 3DNA-DSSR, and images were rendered using PyMOL.
Download the PyMOL session file corresponding to the top-left image in the following panel.

List of 2 5mC-amino acid contacts [summary · schematics · top · homepage · tutorial]

The contacts include paired nucleotides (mostly a G in G-C pairing), and amino-acids within a 4.5-A distance cutoff to the base atoms of 5mC.
The structure is oriented in the 'standard' 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.

	No. 1 D.5CM33: download PDB file for the 5mC entry hydrophobic-with-B.ILE262 is-WC-paired is-in-duplex [+]:AcG/cGT
	No. 2 E.5CM4: download PDB file for the 5mC entry hydrophobic-with-B.VAL269 is-WC-paired is-in-duplex [-]:cGA/TcG