SNAP-annotated 5mC-DNA-protein interactions: PDB entry 4pw7

PDB-id

4pw7; DSSR-derived features in text and JSON formats; DNAproDB

Class

ligase-DNA

Method

X-ray (2.001 Å)

Summary

Structure of uhrf2-sra in complex with a 5mc-containing DNA

Reference

Zhou T, Xiong J, Wang M, Yang N, Wong J, Zhu B, Xu RM (2014): "Structural Basis for Hydroxymethylcytosine Recognition by the SRA Domain of UHRF2." Mol.Cell, 54, 879-886. doi: 10.1016/j.molcel.2014.04.003.

Abstract

Methylated cytosine of CpG dinucleotides in vertebrates may be oxidized by Tet proteins, a process that can lead to DNA demethylation. The predominant oxidation product, 5-hydroxymethylcytosine (5hmC), has been implicated in embryogenesis, cell differentiation, and human diseases. Recently, the SRA domain of UHRF2 (UHRF2-SRA) has been reported to specifically recognize 5hmC, but how UHRF2 recognizes this modification is unclear. Here we report the structure of UHRF2-SRA in complex with a 5hmC-containing DNA. The structure reveals that the conformation of a phenylalanine allows the formation of an optimal 5hmC binding pocket, and a hydrogen bond between the hydroxyl group of 5hmC and UHRF2-SRA is critical for their preferential binding. Further structural and biochemical analyses unveiled the role of SRA domains as a versatile reader of modified DNA, and the knowledge should facilitate further understanding of the biological function of UHRF2 and the comprehension of DNA hydroxymethylation in general.

• 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.