The Role of Histone H3 Leucine 126 as the Axial Copper Ligand
The copper reductase activity of histone H3 suggests the presence of yet-to-be-discovered characteristics within the protein. Here, we investigated the function of leucine 126 (H3L126), which serves as the axial ligand for copper binding. Typically found as a methionine or leucine in copper binding proteins, the axial ligand influences the reduction potential of the bound ion, thereby modulating the capability of a protein to conduct electrons. Mutation of H3L126 to methionine (H3L126M) increased the enzymatic activity of yeast nucleosomes and intracellular Cu1+ levels, leading to improved copper-dependent activities including mitochondrial respiration and growth in oxidative media with low copper. H3L126 to histidine (H3L126H) mutation decreased nucleosome's enzymatic activity and resulted in opposite phenotypes in vivo. Our findings demonstrate the role of H3L126 in fine-tuning the copper reductase activity of nucleosomes and underscore the utility of nucleosome enzymatic activity as a novel paradigm to uncover previously unnoticed features of histones. Overall design: mRNA profiles of yeast with the histone H3 L126M and L126H mutations grown in fermentative and oxidative media