Structural highlights
Function
CALYP_DROME Polycomb group (PcG) protein. Catalytic component of the PR-DUB complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at 'Lys-118' (H2AK118ub1). Does not deubiquitinate monoubiquitinated histone H2B. Required to maintain the transcriptionally repressive state of homeotic genes throughout development. The PR-DUB complex has weak or no activity toward 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.[1]
Publication Abstract from PubMed
Attachment of ubiquitin to lysine 119 of Histone 2A (H2AK119Ub) is an epigenetic mark characteristic of repressed developmental genes, which is removed by the Polycomb Repressive-Deubiquitinase (PR-DUB) complex. Here we report the crystal structure of the Drosophila PR-DUB, revealing that the deubiquitinase Calypso and its activating partner ASX form a 2:2 complex. The bidentate Calypso-ASX complex is generated by dimerisation of two activated Calypso proteins through their coiled-coil regions. Disrupting the Calypso dimer interface does not affect inherent catalytic activity, but inhibits removal of H2AK119Ub as a consequence of impaired recruitment to nucleosomes. Mutating the equivalent surface on the human counterpart, BAP1, also compromises activity on nucleosomes. Together, this suggests that high local concentrations drive assembly of bidentate PR-DUB complexes on chromatin-providing a mechanistic basis for enhanced PR-DUB activity at specific genomic foci, and the impact of distinct classes of PR-DUB mutations in tumorigenesis.
A bidentate Polycomb Repressive-Deubiquitinase complex is required for efficient activity on nucleosomes.,Foglizzo M, Middleton AJ, Burgess AE, Crowther JM, Dobson RCJ, Murphy JM, Day CL, Mace PD Nat Commun. 2018 Sep 26;9(1):3932. doi: 10.1038/s41467-018-06186-1. PMID:30258054[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Scheuermann JC, de Ayala Alonso AG, Oktaba K, Ly-Hartig N, McGinty RK, Fraterman S, Wilm M, Muir TW, Muller J. Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-DUB. Nature. 2010 May 13;465(7295):243-7. doi: 10.1038/nature08966. Epub 2010 May 2. PMID:20436459 doi:http://dx.doi.org/10.1038/nature08966
- ↑ Foglizzo M, Middleton AJ, Burgess AE, Crowther JM, Dobson RCJ, Murphy JM, Day CL, Mace PD. A bidentate Polycomb Repressive-Deubiquitinase complex is required for efficient activity on nucleosomes. Nat Commun. 2018 Sep 26;9(1):3932. doi: 10.1038/s41467-018-06186-1. PMID:30258054 doi:http://dx.doi.org/10.1038/s41467-018-06186-1
