4pw7
From Proteopedia
structure of UHRF2-SRA in complex with a 5mC-containing DNA
Structural highlights
DiseaseUHRF2_HUMAN Associated with various cancers. DNA copy number loss is found in multiple kinds of malignancies originating from the brain, breast, stomach, kidney, hematopoietic tissue and lung. FunctionUHRF2_HUMAN E3 ubiquitin-protein ligase that is an intermolecular hub protein in the cell cycle network. Through cooperative DNA and histone binding, may contribute to a tighter epigenetic control of gene expression in differentiated cells. Ubiquitinates cyclins, CCND1 and CCNE1, in an apparently phosphorylation-independent manner and induces G1 arrest. Also ubiquitinates PCNP leading to its degradation by the proteasome. E3 SUMO-, but not ubiquitin-, protein ligase for ZNF131.[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedMethylated 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. Structural Basis for Hydroxymethylcytosine Recognition by the SRA Domain of UHRF2.,Zhou T, Xiong J, Wang M, Yang N, Wong J, Zhu B, Xu RM Mol Cell. 2014 May 7. pii: S1097-2765(14)00313-X. doi:, 10.1016/j.molcel.2014.04.003. PMID:24813944[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Homo sapiens | Large Structures | Wang M | Wong J | Xiong J | Xu RM | Yang N | ZHou T | Zhu B
