5fr6

The structure of polycomb ULD complexThe structure of polycomb ULD complex

Structural highlights

5fr6 is a 1 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 2.51Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BMI1_HUMAN Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. In the PRC1 complex, it is required to stimulate the E3 ubiquitin-protein ligase activity of RNF2/RING2.^[1] ^[2] ^[3]

Publication Abstract from PubMed

BMI1 is a core component of the polycomb repressive complex 1 (PRC1) and emerging data support a role of BMI1 in cancer. The central domain of BMI1 is involved in protein-protein interactions and is essential for its oncogenic activity. Here, we present the structure of BMI1 bound to the polyhomeotic protein PHC2 illustrating that the central domain of BMI1 adopts an ubiquitin-like (UBL) fold and binds PHC2 in a beta-hairpin conformation. Unexpectedly, we find that the UBL domain is involved in homo-oligomerization of BMI1. We demonstrate that both the interaction of BMI1 with polyhomeotic proteins and homo-oligomerization via UBL domain are necessary for H2A ubiquitination activity of PRC1 and for clonogenic potential of U2OS cells. Here, we also emphasize need for joint application of NMR spectroscopy and X-ray crystallography to determine the overall structure of the BMI1-PHC2 complex.

BMI1 regulates PRC1 architecture and activity through homo- and hetero-oligomerization.,Gray F, Cho HJ, Shukla S, He S, Harris A, Boytsov B, Jaremko L, Jaremko M, Demeler B, Lawlor ER, Grembecka J, Cierpicki T Nat Commun. 2016 Nov 9;7:13343. doi: 10.1038/ncomms13343. PMID:27827373^[4]

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

References

↑ Cao R, Tsukada Y, Zhang Y. Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. Mol Cell. 2005 Dec 22;20(6):845-54. PMID:16359901 doi:10.1016/j.molcel.2005.12.002
↑ Chagraoui J, Niessen SL, Lessard J, Girard S, Coulombe P, Sauvageau M, Meloche S, Sauvageau G. E4F1: a novel candidate factor for mediating BMI1 function in primitive hematopoietic cells. Genes Dev. 2006 Aug 1;20(15):2110-20. PMID:16882984 doi:http://dx.doi.org/20/15/2110
↑ Li Z, Cao R, Wang M, Myers MP, Zhang Y, Xu RM. Structure of a Bmi-1-Ring1B polycomb group ubiquitin ligase complex. J Biol Chem. 2006 Jul 21;281(29):20643-9. Epub 2006 May 18. PMID:16714294 doi:10.1074/jbc.M602461200
↑ Gray F, Cho HJ, Shukla S, He S, Harris A, Boytsov B, Jaremko L, Jaremko M, Demeler B, Lawlor ER, Grembecka J, Cierpicki T. BMI1 regulates PRC1 architecture and activity through homo- and hetero-oligomerization. Nat Commun. 2016 Nov 9;7:13343. doi: 10.1038/ncomms13343. PMID:27827373 doi:http://dx.doi.org/10.1038/ncomms13343

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OCA

[1] Cao R, Tsukada Y, Zhang Y. Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. Mol Cell. 2005 Dec 22;20(6):845-54. PMID:16359901 doi:10.1016/j.molcel.2005.12.002

[2] Chagraoui J, Niessen SL, Lessard J, Girard S, Coulombe P, Sauvageau M, Meloche S, Sauvageau G. E4F1: a novel candidate factor for mediating BMI1 function in primitive hematopoietic cells. Genes Dev. 2006 Aug 1;20(15):2110-20. PMID:16882984 doi:http://dx.doi.org/20/15/2110

[3] Li Z, Cao R, Wang M, Myers MP, Zhang Y, Xu RM. Structure of a Bmi-1-Ring1B polycomb group ubiquitin ligase complex. J Biol Chem. 2006 Jul 21;281(29):20643-9. Epub 2006 May 18. PMID:16714294 doi:10.1074/jbc.M602461200

[4] Gray F, Cho HJ, Shukla S, He S, Harris A, Boytsov B, Jaremko L, Jaremko M, Demeler B, Lawlor ER, Grembecka J, Cierpicki T. BMI1 regulates PRC1 architecture and activity through homo- and hetero-oligomerization. Nat Commun. 2016 Nov 9;7:13343. doi: 10.1038/ncomms13343. PMID:27827373 doi:http://dx.doi.org/10.1038/ncomms13343

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