5IAY

NMR structure of UHRF1 Tandem Tudor Domains in a complex with Spacer peptide

Summary for 5IAY

• Entry DOI: 10.2210/pdb5iay/pdb
• NMR Information: BMRB: 30019
• Descriptor: E3 ubiquitin-protein ligase UHRF1, Spacer (2 entities in total)
• Functional Keywords: uhrf1, ttd, spacer, ligase
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus : Q96T88
• Total number of polymer chains: 2
• Total formula weight: 19411.72

Authors

Fang, J.,Cheng, J.,Wang, J.,Zhang, Q.,Liu, M.,Gong, R.,Wang, P.,Zhang, X.,Feng, Y.,Lan, W.,Gong, Z.,Tang, C.,Wong, J.,Yang, H.,Cao, C.,Xu, Y. (deposition date: 2016-02-22, release date: 2016-04-20, Last modification date: 2024-05-01)

Primary citation

Fang, J.,Cheng, J.,Wang, J.,Zhang, Q.,Liu, M.,Gong, R.,Wang, P.,Zhang, X.,Feng, Y.,Lan, W.,Gong, Z.,Tang, C.,Wong, J.,Yang, H.,Cao, C.,Xu, Y.
Hemi-methylated DNA opens a closed conformation of UHRF1 to facilitate its histone recognition
Nat Commun, 7:11197-11197, 2016

PubMed Abstract: UHRF1 is an important epigenetic regulator for maintenance DNA methylation. UHRF1 recognizes hemi-methylated DNA (hm-DNA) and trimethylation of histone H3K9 (H3K9me3), but the regulatory mechanism remains unknown. Here we show that UHRF1 adopts a closed conformation, in which a C-terminal region (Spacer) binds to the tandem Tudor domain (TTD) and inhibits H3K9me3 recognition, whereas the SET-and-RING-associated (SRA) domain binds to the plant homeodomain (PHD) and inhibits H3R2 recognition. Hm-DNA impairs the intramolecular interactions and promotes H3K9me3 recognition by TTD-PHD. The Spacer also facilitates UHRF1-DNMT1 interaction and enhances hm-DNA-binding affinity of the SRA. When TTD-PHD binds to H3K9me3, SRA-Spacer may exist in a dynamic equilibrium: either recognizes hm-DNA or recruits DNMT1 to chromatin. Our study reveals the mechanism for regulation of H3K9me3 and hm-DNA recognition by URHF1.

PubMed: 27045799
DOI: 10.1038/ncomms11197

Experimental method

SOLUTION NMR