Zinc finger and other zinc-structural proteins (ZNF)

Zinc finger proteins (ZNFs) represent one of the largest and most diverse superfamilies of proteins in the human genome, characterized by small structural motifs stabilized by the coordination of one or more zinc ions [NIH, 2024]. These proteins primarily function as interaction modules that bind to DNA, RNA, or other proteins, making them central regulators of gene expression, chromatin remodeling, and DNA repair [Wikipedia, 2024]. In disease contexts, dysregulation of specific ZNFs like ZEB1 and SNAIL is a hallmark of the epithelial-mesenchymal transition (EMT) in cancer, while others are critical for viral replication, such as the HIV-1 nucleocapsid protein NCp7 [NIH, 2024; Wikipedia, 2024]. Historically considered "undruggable" due to their lack of traditional active sites, ZNFs are now targeted through innovative strategies including zinc-ejecting agents that disrupt the structural fold and thalidomide-based molecular glues that induce their proteasomal degradation [ScienceDaily, 2018; NIH, 2019]. Despite their therapeutic potential, the high abundance and structural similarity among ZNF family members present significant challenges for achieving the selectivity required to avoid systemic toxicity and off-target effects [NIH, 2019; ResearchGate, 2024].

Other names

Zinc finger proteinsZNFsZinc-binding proteinsZinc-structural motifsZinc-coordinated proteins

Zinc ejection (displacement of Zn2+), targeted protein degradation (TPD) via E3 ligase recruitment, inhibition of DNA binding, and transcriptional modulation.