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Human UHRF1, RING domain

PDB Code 3FL2 Target Class Ubiquitylation Target UHRF1 Alias FLJ21925, hNP95, ICBP90, MGC138707, Np95, RNF106 Disease Area/Function Date Deposited Dec 18 2008 Authors Walker JR, Avvakumov GV, Xue S, Li Y, Bountra C, Weigelt J, Arrowsmith CH, Edwards AM, Bochkarev A, Dhe-Paganon S Related Structure 3CLZ, 3DB4, 3DB3

About this structure

Convergence of the ubiquitylation, acetylation, and methylation systems occurs with UHRF1, a nuclear protein containing domains that bind modified histone H3 (via tandem Tudor domain), modified (hemimethylated) DNA (via Set and RING- associated domain, SRA)[1], and catalyze ubiquitylation (via RING domain). This protein is involved in a number of biological events including transcriptional regulation, DNA repair, and epigenetic code inheritance.

It is known that UHRF1 acts as E3 ligase to catalyze ubiquitylation of histone H3[2]. However, the full spectrum of the ubiquitylation substrates of UHRF1 is not known. As a part of the studies to address this issue, we have solved the crystal structure of the RING domain.

The structure of the UHRF1 RING domain reveals the canonical RING fold tightly associated with a helical bundle. Residues 675-722 and 775-786 of UHRF1 form a four-helix antiparallel bundle that flanks the central RING motif. The UHRF1 RING motif is characterized by a central alpha-helix adjacent to a short antiparallel three-stranded beta-sheet with two Zn2+ atoms bound by three zinc-fingers. Identity and conformation of putative E2-binding human UHRF1 side chains are completely conserved with those of human UHRF2 (PDB 1Z6U); this suggests that both UHRF1 and UHRF2 bind to the same set of E2s.

References

  1. Avvakumov, G. V., Walker, J. R., Xue, S., Li, Y., Duan, S., Bronner, C., Arrowsmith, C. H., and Dhe-Paganon, S. (2008) Structural basis for recognition of hemi-methylated DNA by the SRA domain of human UHRF1, Nature.
  2. Karagianni, P., Amazit, L., Qin, J.and Wong, J. (2008) ICBP90, a novel methyl K9 H3 binding protein linking protein ubiquitination with heterochromatin formation. Mol. Cell. Biol., 28, 705-717.