Zhang Houfang, Guo Wenhan, Xu Wang, Li Anbang, Jiang Lijun, Li Lin, Peng Yunhui
Institute of Biophysics and Department of Physics, Central China Normal University, Wuhan 430079, China.
Department of Physics, University of Texas at El Paso, El Paso, Texas 79902, USA.
J Chem Phys. 2025 Mar 14;162(10). doi: 10.1063/5.0252788.
The nucleosome serves as the fundamental unit of chromatin organization, with electrostatic interactions acting as the driving forces in the folding of nucleosomes into chromatin. Perturbations around physiological pH conditions can lead to changes in the protonation states of titratable histone residues, impacting nucleosome surface electrostatic potentials and interactions. However, the effects of proton uptake or release of histone ionizable groups on nucleosome-partner protein interactions and higher-order chromatin structures remain largely unexplored. Here, we conducted comprehensive analyses of histone titratable residue pKa values in various nucleosome contexts, utilizing 96 experimentally determined complex structures. We revealed that pH-induced changes in histone residue protonation states modulated nucleosome surface electrostatic potentials and significantly influenced nucleosome-partner protein interactions. Furthermore, we observed that proton uptake or release often accompanied nucleosome-partner protein interactions, facilitating their binding processes. In addition, our findings suggest that alterations in histone protonation can also regulate nucleosome self-association, thereby modulating the organization and dynamics of higher-order chromatin structure. This study advances our understanding of nucleosome-chromatin factor interactions and how chromatin organization is regulated at the molecular level.
核小体是染色质组织的基本单位，静电相互作用是核小体折叠成染色质的驱动力。生理pH条件附近的扰动可导致可滴定组蛋白残基质子化状态的变化，影响核小体表面静电势和相互作用。然而，组蛋白可电离基团的质子摄取或释放对核小体-伴侣蛋白相互作用和高阶染色质结构的影响在很大程度上仍未得到探索。在这里，我们利用96个实验确定的复杂结构，对各种核小体环境中组蛋白可滴定残基的pKa值进行了全面分析。我们发现，pH诱导的组蛋白残基质子化状态变化调节了核小体表面静电势，并显著影响了核小体-伴侣蛋白相互作用。此外，我们观察到质子摄取或释放常常伴随着核小体-伴侣蛋白相互作用，促进它们的结合过程。此外，我们的研究结果表明，组蛋白质子化的改变也可以调节核小体的自缔合，从而调节高阶染色质结构的组织和动力学。这项研究增进了我们对核小体-染色质因子相互作用以及染色质组织在分子水平上如何被调控的理解。
