6K5W
Solution structure of the chromodomain of yeast Eaf3
6K5W の概要
エントリーDOI | 10.2210/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 | |
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: 32031206DOI: 10.1042/BSR20191958 主引用文献が同じPDBエントリー |
実験手法 | SOLUTION NMR |
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