The copper reductase activity of histone H3 suggests undiscovered characteristics within the protein. Here, we investigated the function of leucine 126 (H3L126), which occupies an axial position relative to the copper binding. Typically found as methionine or leucine in copper-binding proteins, the axial ligand influences the reduction potential of the bound ion, modulating its tendency to accept or yield electrons. We found that mutation of H3L126 to methionine (H3L126M) enhanced the enzymatic activity of native yeast nucleosomes and increased intracellular levels of Cu, leading to improved copper-dependent activities including mitochondrial respiration and growth in oxidative media with low copper. Conversely, H3L126 to histidine (H3L126H) mutation decreased nucleosome’s enzymatic activity and adversely affected copper-dependent activities . Our findings demonstrate that H3L126 fine-tunes the copper reductase activity of nucleosomes and highlights the utility of nucleosome enzymatic activity as a novel paradigm to uncover previously unnoticed features of histones.

中文翻译：

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组蛋白 H3 亮氨酸 126 在微调核小体铜还原酶活性中的作用


组蛋白 H3 的铜还原酶活性表明该蛋白质具有未被发现的特征。在这里，我们研究了亮氨酸 126 (H3L126) 的功能，它占据相对于铜结合的轴向位置。轴向配体通常在铜结合蛋白中以蛋氨酸或亮氨酸形式存在，它影响结合离子的还原电位，调节其接受或产生电子的倾向。我们发现，H3L126 突变为甲硫氨酸 (H3L126M) 增强了天然酵母核小体的酶活性，并增加了细胞内铜的水平，从而改善了铜依赖性活动，包括线粒体呼吸和在低铜氧化介质中的生长。相反，H3L126 突变为组氨酸（H3L126H）会降低核小体的酶活性并对铜依赖性活性产生不利影响。我们的研究结果表明，H3L126 微调核小体的铜还原酶活性，并强调核小体酶活性作为一种新范例的效用，以揭示以前未被注意到的组蛋白特征。