The presence of Zn²⁺ at protein–protein interfaces modulates complex function, stability, and introduces structural flexibility/complexity, chemical selectivity, and reversibility driven in a Zn²⁺-dependent manner. Recent studies have demonstrated that dynamically changing Zn²⁺ affects numerous cellular processes, including protein–protein communication and protein complex assembly. How Zn²⁺-involved protein–protein interactions (ZPPIs) are formed and dissociate and how their stability and reactivity are driven in a zinc interactome remain poorly understood, mostly due to experimental obstacles. Here, we review recent research advances on the role of Zn²⁺ in the formation of interprotein sites, their architecture, function, and stability. Moreover, we underline the importance of zinc networks in intersystemic communication and highlight bioinformatic and experimental challenges required for the identification and investigation of ZPPIs.

蛋白质-蛋白质界面上Zn ²⁺的存在调节了复杂的功能，稳定性，并引入了依赖于Zn ^2+的方式驱动的结构柔性/复杂性，化学选择性和可逆性。最近的研究表明，动态变化的Zn ²⁺会影响许多细胞过程，包括蛋白质-蛋白质通讯和蛋白质复合物装配。Zn ²⁺参与的蛋白质-蛋白质相互作用（ZPPI）如何形成和分离以及如何在锌相互作用组中驱动其稳定性和反应性仍知之甚少，主要是由于实验障碍。在这里，我们回顾了有关Zn ²⁺的作用的最新研究进展。在蛋白间位点的形成，其结构，功能和稳定性方面。此外，我们强调了锌网络在系统间通讯中的重要性，并强调了识别和研究ZPPI所需的生物信息学和实验挑战。