Structure of the UHRF1 Tandem Tudor Domain Bound to a Methylated Non-histone Protein, LIG1, Reveals Rules for Binding and Regulation.
The protein UHRF1 is crucial for DNA methylation maintenance. The tandem Tudor domain (TTD) of UHRF1 binds histone H3K9me2/3 with micromolar affinity, as well as unmethylated linker regions within UHRF1 itself, causing auto-inhibition. Recently, we showed that a methylated histone-like region of DNA ligase 1 (LIG1K126me2/me3) binds the UHRF1 TTD ... with nanomolar affinity, permitting UHRF1 recruitment to chromatin. Here we report the crystal structure of the UHRF1 TTD bound to a LIG1K126me3 peptide. The data explain the basis for the high TTD-binding affinity of LIG1K126me3 and reveal that the interaction may be regulated by phosphorylation. Binding of LIG1K126me3 switches the overall structure of UHRF1 from a closed to a flexible conformation, suggesting that auto-inhibition is relieved. Our results provide structural insight into how UHRF1 performs its key function in epigenetic maintenance.
Mesh Terms:
Arginine, Binding Sites, CCAAT-Enhancer-Binding Proteins, Crystallography, X-Ray, DNA Ligase ATP, Epigenesis, Genetic, Gene Expression Regulation, Histones, Humans, Methylation, Models, Molecular, Phosphorylation, Protein Conformation, Protein Domains, Ubiquitin-Protein Ligases
Arginine, Binding Sites, CCAAT-Enhancer-Binding Proteins, Crystallography, X-Ray, DNA Ligase ATP, Epigenesis, Genetic, Gene Expression Regulation, Histones, Humans, Methylation, Models, Molecular, Phosphorylation, Protein Conformation, Protein Domains, Ubiquitin-Protein Ligases
Structure
Date: Dec. 05, 2018
PubMed ID: 30639225
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