组蛋白 1 同种型 4 赖氨酸 26 的 KDM 催化去甲基化的机制和结构研究。
Mechanistic and structural studies of KDM-catalysed demethylation of histone 1 isotype 4 at lysine 26.
机构信息
Department of Chemistry, Chemistry Research Laboratory, University of Oxford, UK.
Leicester Institute of Structural and Chemical Biology and Department of Chemistry, University of Leicester, UK.
出版信息
FEBS Lett. 2018 Oct;592(19):3264-3273. doi: 10.1002/1873-3468.13231. Epub 2018 Sep 14.
N-Methylation of lysyl residues is widely observed on histone proteins. Using isolated enzymes, we report mechanistic and structural studies on histone lysine demethylase (KDM)-catalysed demethylation of N -methylated lysine 26 on histone 1 isotype 4 (H1.4). The results reveal that methylated H1.4K26 is a substrate for all members of the KDM4 subfamily and that KDM4A-catalysed demethylation of H1.4K26me3 peptide is similarly efficient to that of H3K9me3. Crystallographic studies of an H1.4K26me3:KDM4A complex reveal a conserved binding geometry to that of H3K9me3. In the light of the high activity of the KDM4s on this mark, our results suggest JmjC KDM-catalysed demethylation of H1.4K26 may be as prevalent as demethylation on the H3 tail and warrants further investigation in cells.
赖氨酸残基的 N-甲基化在组蛋白蛋白上广泛存在。使用分离的酶，我们报告了组蛋白赖氨酸去甲基酶（KDM）催化的组蛋白 1 同种型 4（H1.4）上 N-甲基化赖氨酸 26 的去甲基化的机制和结构研究。结果表明，甲基化的 H1.4K26 是 KDM4 亚家族所有成员的底物，并且 KDM4A 催化的 H1.4K26me3 肽的去甲基化与 H3K9me3 的去甲基化同样有效。H1.4K26me3：KDM4A 复合物的晶体学研究揭示了与 H3K9me3 的保守结合几何形状。鉴于 KDM4 对该标记的高活性，我们的结果表明 JmjC KDM 催化的 H1.4K26 去甲基化可能与 H3 尾部的去甲基化一样普遍，值得在细胞中进一步研究。
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