6B9M

Crystal structure of UHRF1 TTD domain in complex with the polybasic region

Summary for 6B9M

• Entry DOI: 10.2210/pdb6b9m/pdb
• Descriptor: E3 ubiquitin-protein ligase UHRF1 (3 entities in total)
• Functional Keywords: complex, transferase
• Biological source: Danio rerio (Zebrafish); More
• Cellular location: Nucleus : E7EZF3 Q96T88
• Total number of polymer chains: 4
• Total formula weight: 57677.97

Authors

Song, J.,Tan, X. (deposition date: 2017-10-10, release date: 2018-02-14, Last modification date: 2024-03-13)

Primary citation

Gao, L.,Tan, X.F.,Zhang, S.,Wu, T.,Zhang, Z.M.,Ai, H.W.,Song, J.
An Intramolecular Interaction of UHRF1 Reveals Dual Control for Its Histone Association.
Structure, 26:304-311.e3, 2018

PubMed Abstract: UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1) is one of the essential components of mammalian DNA methylation machinery. Chromatin association of UHRF1 is controlled via an interplay between its intramolecular interaction and dual recognition of histone H3 trimethylated at lysine 9 (H3K9me3) and hemimethylated DNA. Here, we report the crystal structure of the N-terminal tandem Tudor domain (TTD) of UHRF1 in complex with the C-terminal polybasic region (PBR). Structural analysis reveals that PBR binding leads to displacement of the TTD-plant homeodomain (PHD) linker, as well as blockage of the H3K9me3-engaging cage, both of which contribute to a chromatin-occluded UHRF1 conformation. Disruption of the TTD-PBR interaction, which is facilitated by the binding of UHRF1 to hemimethylated DNA or regulatory protein USP7, shifts the UHRF1 conformation toward an open state, allowing for efficient H3K9me3 binding. Together, this study provides structural basis for the allosteric regulation of UHRF1.

PubMed: 29395786
DOI: 10.1016/j.str.2017.12.016

Experimental method

X-RAY DIFFRACTION (1.68 Å)