Metal binding properties, stability and reactivity of zinc fingers

Zinc fingers (ZFs) are among the most structurally diverse protein domains. They interact with nucleic acids, other proteins and lipids to facilitate a multitude of biological processes. Currently, there are more than 10 known classes of ZFs, with various architectures, metal binding modes, functions and reactivity. The versatility, selectivity and stability of these short amino acid sequences is achieved mainly by (i) residues participating in Zn(II) coordination (mostly Cys and His), (ii) hydrophobic core and ZF structure formation, and (iii) variable residues responsible for inter- and intramolecular interactions. Since their discovery, ZFs have been extensively studied in terms of their structure, stability and recognition targets by the application of various methodologies. Studies based on interactions with other metal ions and their complexes have contributed to the understanding of their chemical properties and the discovery of new types of ZF complexes, such as gold fingers or lead fingers. Moreover, due to the presence of nucleophilic thiolates, ZFs are targets for reactive oxygen and nitrogen species as well as alkylating agents. Interactions with many reactive molecules lead to disturb the native Zn(II) coordination site which further result in structural and functional damage of the ZFs. The post-translational modifications including phosphorylation, acetylation, methylation or nitrosylation frequently affect ZFs function via changes in the protein structure and dynamics. Even though the literature is replete with structural and stability data regarding classical (ββα) ZFs, there is still a huge gap in the knowledge on physicochemical properties and reactivity of other ZF types. In this review, metal binding properties of ZFs and stability factors that modulate their functions are reviewed. These include interactions of ZFs with biogenic and toxic metal ions as well as damage occurring upon reaction with reactive oxygen and nitrogen species, the methodology used for ZFs characterization, and aspects related to coordination chemistry.