5YY9

Crystal structure of Tandem Tudor Domain of human UHRF1 in complex with LIG1-K126me3

Summary for 5YY9

• Entry DOI: 10.2210/pdb5yy9/pdb
• Descriptor: E3 ubiquitin-protein ligase UHRF1, Ligase 1 (3 entities in total)
• Functional Keywords: maintenance of dna methylation, transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 39604.56

Authors

Kori, S.,Defossez, P.A.,Arita, K. (deposition date: 2017-12-08, release date: 2018-12-12, Last modification date: 2023-11-22)

Primary citation

Kori, S.,Ferry, L.,Matano, S.,Jimenji, T.,Kodera, N.,Tsusaka, T.,Matsumura, R.,Oda, T.,Sato, M.,Dohmae, N.,Ando, T.,Shinkai, Y.,Defossez, P.A.,Arita, K.
Structure of the UHRF1 Tandem Tudor Domain Bound to a Methylated Non-histone Protein, LIG1, Reveals Rules for Binding and Regulation.
Structure, 27:485-, 2019

PubMed Abstract: 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.

PubMed: 30639225
DOI: 10.1016/j.str.2018.11.012

Experimental method

X-RAY DIFFRACTION (2.653 Å)