5MTO

N-terminal domain of the human tumor suppressor ING5 C19S mutant

5MTO の概要

• エントリーDOI: 10.2210/pdb5mto/pdb
• 関連するPDBエントリー: 5MTO
• 分子名称: Inhibitor of growth protein 5, SODIUM ION, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: ing5, tumor suppressor, signaling protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 25211.45

構造登録者

Ormaza, G.,Buitrago, J.A.R.,Roversi, P.,Rojas, A.L.,Blanco, F.J. (登録日: 2017-01-10, 公開日: 2018-02-28, 最終更新日: 2024-01-17)

主引用文献

Ormaza, G.,Rodriguez, J.A.,Ibanez de Opakua, A.,Merino, N.,Villate, M.,Gorrono, I.,Rabano, M.,Palmero, I.,Vilaseca, M.,Kypta, R.,Vivanco, M.D.M.,Rojas, A.L.,Blanco, F.J.
The Tumor Suppressor ING5 Is a Dimeric, Bivalent Recognition Molecule of the Histone H3K4me3 Mark.
J.Mol.Biol., 431:2298-2319, 2019

PubMed Abstract: The INhibitor of Growth (ING) family of tumor suppressors regulates the transcriptional state of chromatin by recruiting remodeling complexes to sites with histone H3 trimethylated at lysine 4 (H3K4me3). This modification is recognized by the plant homeodomain (PHD) present at the C-terminus of the five ING proteins. ING5 facilitates histone H3 acetylation by the HBO1 complex, and also H4 acetylation by the MOZ/MORF complex. We show that ING5 forms homodimers through its N-terminal domain, which folds independently into an elongated coiled-coil structure. The central region of ING5, which contains the nuclear localization sequence, is flexible and disordered, but it binds dsDNA with micromolar affinity. NMR analysis of the full-length protein reveals that the two PHD fingers of the dimer are chemically equivalent and independent of the rest of the molecule, and they bind H3K4me3 in the same way as the isolated PHD. We have observed that ING5 can form heterodimers with the highly homologous ING4, and that two of three primary tumor-associated mutants in the N-terminal domain strongly destabilize the coiled-coil structure. They also affect cell proliferation and cell cycle phase distribution, suggesting a driver role in cancer progression.

PubMed: 31026448
DOI: 10.1016/j.jmb.2019.04.018

実験手法

X-RAY DIFFRACTION (3.1 Å)