8GE0

Crystal structure of JADE1 PZP domain in complex with Histone H3

Summary for 8GE0

• Entry DOI: 10.2210/pdb8ge0/pdb
• Descriptor: Histone H3.1,Protein Jade-1, ZINC ION (3 entities in total)
• Functional Keywords: histone acetylation, transcription activation, nucleosome, pvhl, transcription
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 63405.52

Authors

Klein, B.J.,Liu, J.,Kutateladze, T.G. (deposition date: 2023-03-06, release date: 2024-03-13, Last modification date: 2024-07-31)

Primary citation

Gaurav, N.,Kanai, A.,Lachance, C.,Cox, K.L.,Liu, J.,Grzybowski, A.T.,Saksouk, N.,Klein, B.J.,Komata, Y.,Asada, S.,Ruthenburg, A.J.,Poirier, M.G.,Cote, J.,Yokoyama, A.,Kutateladze, T.G.
Guiding the HBO1 complex function through the JADE subunit.
Nat.Struct.Mol.Biol., 31:1039-1049, 2024

PubMed Abstract: 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.

PubMed: 38448574
DOI: 10.1038/s41594-024-01245-2

Experimental method

X-RAY DIFFRACTION (2.4 Å)