2ZO2

Mouse NP95 SRA domain non-specific DNA complex

Summary for 2ZO2

• Entry DOI: 10.2210/pdb2zo2/pdb
• Related: 2ZO0 2ZO1
• Descriptor: E3 ubiquitin-protein ligase UHRF1, DNA (5'-D(*DAP*DAP*DCP*DTP*DGP*DCP*DGP*DCP*DAP*DGP*DTP*DT)-3'), PHOSPHATE ION (3 entities in total)
• Functional Keywords: base flipping, cell cycle, developmental protein, dna damage, dna repair, dna-binding, ligase, metal-binding, nucleus, phosphoprotein, transcription, transcription regulation, ubl conjugation, ubl conjugation pathway, zinc, zinc-finger, ligase-dna complex, ligase/dna
• Biological source: Mus musculus (mouse)
• Cellular location: Nucleus: Q8VDF2
• Total number of polymer chains: 3
• Total formula weight: 31335.49

Authors

Hashimoto, H.,Horton, J.R.,Cheng, X. (deposition date: 2008-05-05, release date: 2008-09-09, Last modification date: 2023-11-01)

Primary citation

Hashimoto, H.,Horton, J.R.,Zhang, X.,Bostick, M.,Jacobsen, S.E.,Cheng, X.
The SRA domain of UHRF1 flips 5-methylcytosine out of the DNA helix
Nature, 455:826-829, 2008

PubMed Abstract: Maintenance methylation of hemimethylated CpG dinucleotides at DNA replication forks is the key to faithful mitotic inheritance of genomic methylation patterns. UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1) is required for maintenance methylation by interacting with DNA nucleotide methyltransferase 1 (DNMT1), the maintenance methyltransferase, and with hemimethylated CpG, the substrate for DNMT1 (refs 1 and 2). Here we present the crystal structure of the SET and RING-associated (SRA) domain of mouse UHRF1 in complex with DNA containing a hemimethylated CpG site. The DNA is contacted in both the major and minor grooves by two loops that penetrate into the middle of the DNA helix. The 5-methylcytosine has flipped completely out of the DNA helix and is positioned in a binding pocket with planar stacking contacts, Watson-Crick polar hydrogen bonds and van der Waals interactions specific for 5-methylcytosine. Hence, UHRF1 contains a previously unknown DNA-binding module and is the first example of a non-enzymatic, sequence-specific DNA-binding protein domain to use the base flipping mechanism to interact with DNA.

PubMed: 18772888
DOI: 10.1038/nature07280

Experimental method

X-RAY DIFFRACTION (3.09 Å)