4PW6

structure of UHRF2-SRA in complex with a 5hmC-containing DNA, complex II

Summary for 4PW6

• Entry DOI: 10.2210/pdb4pw6/pdb
• Related: 4PW5
• Descriptor: E3 ubiquitin-protein ligase UHRF2, 5hmC-containing DNA1, 5hmC-containing DNA2 (3 entities in total)
• Functional Keywords: sra, 5hmc binding, 5hmc-containing dna, hydroxymethylation, nuclear, ligase-dna complex, ligase/dna
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q96PU4
• Total number of polymer chains: 4
• Total formula weight: 58513.34

Authors

Zhou, T.,Xiong, J.,Wang, M.,Yang, N.,Wong, J.,Zhu, B.,Xu, R.M. (deposition date: 2014-03-18, release date: 2014-05-07, Last modification date: 2023-09-20)

Primary citation

Zhou, T.,Xiong, J.,Wang, M.,Yang, N.,Wong, J.,Zhu, B.,Xu, R.M.
Structural Basis for Hydroxymethylcytosine Recognition by the SRA Domain of UHRF2.
Mol.Cell, 54:879-886, 2014

PubMed 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.

PubMed: 24813944
DOI: 10.1016/j.molcel.2014.04.003

Experimental method

X-RAY DIFFRACTION (3.789 Å)