Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, 100190, China.
Songshan Lake Materials Laboratory, Dongguan, Guangdong, 523808, China.
Adv Sci (Weinh). 2024 Nov;11(42):e2401838. doi: 10.1002/advs.202401838. Epub 2024 Sep 20.
Protein surfaces have pivotal roles in interactions between proteins and other biological molecules. However, the structural dynamics of protein surfaces have rarely been explored and are poorly understood. Here, the surface of a single-stranded DNA (ssDNA) binding protein (SSB) with four DNA binding domains that bind ssDNA in binding site sizes of 35, 56, and 65 nucleotides per tetramer is investigated. Using oligonucleotides as probes to sense the charged surface, NaCl induces a two-state structural transition on the SSB surface even at moderate concentrations. Chelation of sodium ions with charged amino acids alters the network of hydrogen bonds and/or salt bridges on the surface. Such changes are associated with changes in the electrostatic potential landscape and interaction mode. These findings advance the understanding of the molecular mechanism underlying the enigmatic salt-induced transitions between different DNA binding site sizes of SSBs. This work demonstrates that monovalent salt is a key regulator of biomolecular interactions that not only play roles in non-specific electrostatic screening effects as usually assumed but also may configure the surface of proteins to contribute to the effective regulation of biomolecular recognition and other downstream events.
蛋白质表面在蛋白质与其他生物分子的相互作用中起着关键作用。然而，蛋白质表面的结构动态很少被探索，也理解得很差。在这里，研究了一种具有四个 DNA 结合域的单链 DNA（ssDNA）结合蛋白（SSB）的表面，该蛋白结合域的大小为每个四聚体 35、56 和 65 个核苷酸。使用寡核苷酸作为探针来探测带电表面，即使在中等浓度下，NaCl 也会在 SSB 表面诱导出两态结构转变。带电荷的氨基酸螯合钠离子会改变表面上氢键和/或盐桥的网络。这些变化与静电势景观和相互作用模式的变化有关。这些发现推进了对 SSB 不同 DNA 结合位点大小之间神秘的盐诱导转变的分子机制的理解。这项工作表明，单价盐是生物分子相互作用的关键调节剂，它不仅在通常假设的非特异性静电屏蔽效应中发挥作用，而且还可以配置蛋白质表面，有助于有效调节生物分子识别和其他下游事件。
