8ge0

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Crystal structure of JADE1 PZP domain in complex with Histone H3

Structural highlights

8ge0 is a 3 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 2.4Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

JADE1_HUMAN Scaffold subunit of some HBO1 complexes, which have a histone H4 acetyltransferase activity (PubMed:16387653, PubMed:19187766, PubMed:20129055, PubMed:24065767). Plays a key role in HBO1 complex by directing KAT7/HBO1 specificity towards histone H4 acetylation (H4K5ac, H4K8ac and H4K12ac), regulating DNA replication initiation, regulating DNA replication initiation (PubMed:20129055, PubMed:24065767). May also promote acetylation of nucleosomal histone H4 by KAT5 (PubMed:15502158). Promotes apoptosis (PubMed:16046545). May act as a renal tumor suppressor (PubMed:16046545). Negatively regulates canonical Wnt signaling; at least in part, cooperates with NPHP4 in this function (PubMed:22654112).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] H31_HUMAN

Publication Abstract from PubMed

JADE is a core subunit of the HBO1 acetyltransferase complex that regulates developmental and epigenetic programs and promotes gene transcription. Here we describe the mechanism by which JADE facilitates recruitment of the HBO1 complex to chromatin and mediates its enzymatic activity. Structural, genomic and complex assembly in vivo studies show that the PZP (PHD1-zinc-knuckle-PHD2) domain of JADE engages the nucleosome through binding to histone H3 and DNA and is necessary for the association with chromatin targets. Recognition of unmethylated H3K4 by PZP directs enzymatic activity of the complex toward histone H4 acetylation, whereas H3K4 hypermethylation alters histone substrate selectivity. We demonstrate that PZP contributes to leukemogenesis, augmenting transforming activity of the NUP98-JADE2 fusion. Our findings highlight biological consequences and the impact of the intact JADE subunit on genomic recruitment, enzymatic function and pathological activity of the HBO1 complex.

Guiding the HBO1 complex function through the JADE subunit.,Gaurav N, Kanai A, Lachance C, Cox KL, Liu J, Grzybowski AT, Saksouk N, Klein BJ, Komata Y, Asada S, Ruthenburg AJ, Poirier MG, Cote J, Yokoyama A, Kutateladze TG Nat Struct Mol Biol. 2024 Jul;31(7):1039-1049. doi: 10.1038/s41594-024-01245-2. , Epub 2024 Mar 6. PMID:38448574^[8]

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

References

↑ Panchenko MV, Zhou MI, Cohen HT. von Hippel-Lindau partner Jade-1 is a transcriptional co-activator associated with histone acetyltransferase activity. J Biol Chem. 2004 Dec 31;279(53):56032-41. PMID:15502158 doi:10.1074/jbc.M410487200
↑ Zhou MI, Foy RL, Chitalia VC, Zhao J, Panchenko MV, Wang H, Cohen HT. Jade-1, a candidate renal tumor suppressor that promotes apoptosis. Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):11035-40. PMID:16046545 doi:10.1073/pnas.0500757102
↑ Doyon Y, Cayrou C, Ullah M, Landry AJ, Cote V, Selleck W, Lane WS, Tan S, Yang XJ, Cote J. ING tumor suppressor proteins are critical regulators of chromatin acetylation required for genome expression and perpetuation. Mol Cell. 2006 Jan 6;21(1):51-64. PMID:16387653 doi:10.1016/j.molcel.2005.12.007
↑ Saksouk N, Avvakumov N, Champagne KS, Hung T, Doyon Y, Cayrou C, Paquet E, Ullah M, Landry AJ, Côté V, Yang XJ, Gozani O, Kutateladze TG, Côté J. HBO1 HAT complexes target chromatin throughout gene coding regions via multiple PHD finger interactions with histone H3 tail. Mol Cell. 2009 Jan 30;33(2):257-65. PMID:19187766 doi:10.1016/j.molcel.2009.01.007
↑ Miotto B, Struhl K. HBO1 histone acetylase activity is essential for DNA replication licensing and inhibited by Geminin. Mol Cell. 2010 Jan 15;37(1):57-66. PMID:20129055 doi:10.1016/j.molcel.2009.12.012
↑ Borgal L, Habbig S, Hatzold J, Liebau MC, Dafinger C, Sacarea I, Hammerschmidt M, Benzing T, Schermer B. The ciliary protein nephrocystin-4 translocates the canonical Wnt regulator Jade-1 to the nucleus to negatively regulate β-catenin signaling. J Biol Chem. 2012 Jul 20;287(30):25370-80. PMID:22654112 doi:10.1074/jbc.M112.385658
↑ Lalonde ME, Avvakumov N, Glass KC, Joncas FH, Saksouk N, Holliday M, Paquet E, Yan K, Tong Q, Klein BJ, Tan S, Yang XJ, Kutateladze TG, Cote J. Exchange of associated factors directs a switch in HBO1 acetyltransferase histone tail specificity. Genes Dev. 2013 Sep 15;27(18):2009-24. doi: 10.1101/gad.223396.113. PMID:24065767 doi:http://dx.doi.org/10.1101/gad.223396.113
↑ Gaurav N, Kanai A, Lachance C, Cox KL, Liu J, Grzybowski AT, Saksouk N, Klein BJ, Komata Y, Asada S, Ruthenburg AJ, Poirier MG, Côté J, Yokoyama A, Kutateladze TG. Guiding the HBO1 complex function through the JADE subunit. Nat Struct Mol Biol. 2024 Jul;31(7):1039-1049. PMID:38448574 doi:10.1038/s41594-024-01245-2