5mC interactions in PDB entry 5EF6 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]

X-ray (3.0 Å)
Structure of hoxb13 complex with methylated DNA
List of 8 5mC-amino acid contacts:
  1. C.5CM11: hydrophobic-with-A.ILE262 is-WC-paired is-in-duplex [+]:AcG/cGT
  2. F.5CM7: hydrophobic-with-A.VAL269 is-WC-paired is-in-duplex [-]:cGA/TcG
  3. D.5CM11: hydrophobic-with-B.ILE262 is-WC-paired is-in-duplex [+]:AcG/cGT
  4. E.5CM7: hydrophobic-with-B.VAL269 is-WC-paired is-in-duplex [-]:cGG/CcG
  5. H.5CM11: hydrophobic-with-G.ILE262 is-WC-paired is-in-duplex [+]:AcG/cGT
  6. I.5CM7: hydrophobic-with-G.VAL269 is-WC-paired is-in-duplex [-]:cGG/CcG
  7. K.5CM11: hydrophobic-with-J.ILE262 is-WC-paired is-in-duplex [+]:AcG/cGT
  8. L.5CM7: hydrophobic-with-J.VAL269 is-WC-paired is-in-duplex [-]:cGG/CcG
direct SNAP output · DNAproDB 2.0
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
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.

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List of 8 5mC-amino acid contacts [summary · schematics · top · homepage · tutorial]

No. 1 C.5CM11: download PDB file for the 5mC entry
hydrophobic-with-A.ILE262 is-WC-paired is-in-duplex [+]:AcG/cGT
No. 2 F.5CM7: download PDB file for the 5mC entry
hydrophobic-with-A.VAL269 is-WC-paired is-in-duplex [-]:cGA/TcG
No. 3 D.5CM11: download PDB file for the 5mC entry
hydrophobic-with-B.ILE262 is-WC-paired is-in-duplex [+]:AcG/cGT
No. 4 E.5CM7: download PDB file for the 5mC entry
hydrophobic-with-B.VAL269 is-WC-paired is-in-duplex [-]:cGG/CcG
No. 5 H.5CM11: download PDB file for the 5mC entry
hydrophobic-with-G.ILE262 is-WC-paired is-in-duplex [+]:AcG/cGT
No. 6 I.5CM7: download PDB file for the 5mC entry
hydrophobic-with-G.VAL269 is-WC-paired is-in-duplex [-]:cGG/CcG
No. 7 K.5CM11: download PDB file for the 5mC entry
hydrophobic-with-J.ILE262 is-WC-paired is-in-duplex [+]:AcG/cGT
No. 8 L.5CM7: download PDB file for the 5mC entry
hydrophobic-with-J.VAL269 is-WC-paired is-in-duplex [-]:cGG/CcG