Galvanization of Protein-Protein Interactions in a Dynamic Zinc Interactome

Abstract

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.

Keywords: interprotein metal binding site; metal affinity; metalloprotein; zinc buffering; zinc fluctuations.