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6K5W

Solution structure of the chromodomain of yeast Eaf3

6K5W の概要
エントリーDOI10.2210/pdb6k5w/pdb
分子名称Chromatin modification-related protein EAF3 (1 entity in total)
機能のキーワードnuclear protein, histone acetyl transferase, histone deacetylase, transcription
由来する生物種Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
タンパク質・核酸の鎖数1
化学式量合計14103.01
構造登録者
Okuda, M.,Nishimura, Y. (登録日: 2019-05-31, 公開日: 2020-02-26, 最終更新日: 2024-05-15)
主引用文献Okuda, M.,Nishimura, Y.
The Eaf3 chromodomain acts as a pH sensor for gene expression by altering its binding affinity for histone methylated-lysine residues.
Biosci.Rep., 40:-, 2020
Cited by
PubMed Abstract: During gene expression, histone acetylation by histone acetyltransferase (HAT) loosens the chromatin structure around the promoter to allow RNA polymerase II (Pol II) to initiate transcription, while de-acetylation by histone deacetylase (HDAC) tightens the structure in the transcribing region to repress false initiation. Histone acetylation is also regulated by intracellular pH (pHi) with global hypoacetylation observed at low pHi, and hyperacetylation, causing proliferation, observed at high pHi. However, the mechanism underlying the pHi-dependent regulation of gene expression remains elusive. Here, we have explored the role of the chromodomain (CD) of budding yeast Eaf3, a common subunit of both HAT and HDAC that is thought to recognize methylated lysine residues on histone H3. We found that Eaf3 CD interacts with histone H3 peptides methylated at Lys4 (H3K4me, a promoter epigenetic marker) and Lys36 (H3K36me, a coding region epigenetic marker), as well as with many dimethyl-lysine peptides and even arginine-asymmetrically dimethylated peptides, but not with unmethylated, phosphorylated or acetylated peptides. The Eaf3 CD structure revealed an unexpected histidine residue in the aromatic cage essential for binding H3K4me and H3K36me. pH titration experiments showed that protonation of the histidine residue around physiological pH controls the charge state of the aromatic cage to regulate binding to H3K4me and H3K36me. Histidine substitution and NMR experiments confirmed the correlation of histidine pKa with binding affinity. Collectively, our findings suggest that Eaf3 CD functions as a pHi sensor and a regulator of gene expression via its pHi-dependent interaction with methylated nucleosomes.
PubMed: 32031206
DOI: 10.1042/BSR20191958
主引用文献が同じPDBエントリー
実験手法
SOLUTION NMR
構造検証レポート
Validation report summary of 6k5w
検証レポート(詳細版)ダウンロードをダウンロード

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件を2024-11-13に公開中

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