Structural Basis for the Hierarchical Assembly of the Core of PRC1.1Structural Basis for the Hierarchical Assembly of the Core of PRC1.1

Structural highlights

5jh5 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.55Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KDM2B_HUMAN Histone demethylase that demethylates 'Lys-4' and 'Lys-36' of histone H3, thereby playing a central role in histone code. Preferentially demethylates trimethylated H3 'Lys-4' and dimethylated H3 'Lys-36' residue while it has weak or no activity for mono- and tri-methylated H3 'Lys-36'. Preferentially binds the transcribed region of ribosomal RNA and represses the transcription of ribosomal RNA genes which inhibits cell growth and proliferation. May also serve as a substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex.[1] [2]

Publication Abstract from PubMed

KDM2B recruits H2A-ubiquitinating activity of a non-canonical Polycomb Repression Complex 1 (PRC1.1) to CpG islands, facilitating gene repression. We investigated the molecular basis of recruitment using in vitro assembly assays to identify minimal components, subcomplexes, and domains required for recruitment. A minimal four-component PRC1.1 complex can be assembled by combining two separately isolated subcomplexes: the DNA-binding KDM2B/SKP1 heterodimer and the heterodimer of BCORL1 and PCGF1, a core component of PRC1.1. The crystal structure of the KDM2B/SKP1/BCORL1/PCGF1 complex illustrates the crucial role played by the PCGF1/BCORL1 heterodimer. The BCORL1 PUFD domain positions residues preceding the RAWUL domain of PCGF1 to create an extended interface for interaction with KDM2B, which is unique to the PCGF1-containing PRC1.1 complex. The structure also suggests how KDM2B might simultaneously function in PRC1.1 and an SCF ubiquitin ligase complex and the possible molecular consequences of BCOR PUFD internal tandem duplications found in pediatric kidney and brain tumors.

KDM2B Recruitment of the Polycomb Group Complex, PRC1.1, Requires Cooperation between PCGF1 and BCORL1.,Wong SJ, Gearhart MD, Taylor AB, Nanyes DR, Ha DJ, Robinson AK, Artigas JA, Lee OJ, Demeler B, Hart PJ, Bardwell VJ, Kim CA Structure. 2016 Aug 23. pii: S0969-2126(16)30222-2. doi:, 10.1016/j.str.2016.07.011. PMID:27568929[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Tsukada Y, Fang J, Erdjument-Bromage H, Warren ME, Borchers CH, Tempst P, Zhang Y. Histone demethylation by a family of JmjC domain-containing proteins. Nature. 2006 Feb 16;439(7078):811-6. Epub 2005 Dec 18. PMID:16362057 doi:http://dx.doi.org/nature04433
  2. Frescas D, Guardavaccaro D, Bassermann F, Koyama-Nasu R, Pagano M. JHDM1B/FBXL10 is a nucleolar protein that represses transcription of ribosomal RNA genes. Nature. 2007 Nov 8;450(7167):309-13. PMID:17994099 doi:http://dx.doi.org/nature06255
  3. Wong SJ, Gearhart MD, Taylor AB, Nanyes DR, Ha DJ, Robinson AK, Artigas JA, Lee OJ, Demeler B, Hart PJ, Bardwell VJ, Kim CA. KDM2B Recruitment of the Polycomb Group Complex, PRC1.1, Requires Cooperation between PCGF1 and BCORL1. Structure. 2016 Aug 23. pii: S0969-2126(16)30222-2. doi:, 10.1016/j.str.2016.07.011. PMID:27568929 doi:http://dx.doi.org/10.1016/j.str.2016.07.011

5jh5, resolution 2.55Å

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