Structural metal sites in nonclassical zinc finger proteins involved in transcriptional and translational regulation.

ConspectusZinc finger (ZF) proteins are a large family of metalloproteins that utilize zinc for structural purposes. Zinc coordinates to a combination of cysteine thiol and histidine imidazole residues within the ZF polypeptide sequence resulting in a folded and functional protein. Initially, a single class of ZFs were identified. These ZFs, now referred to as the “classical” ZFs, utilize a Cys2His2 (CCHH) ligand set to bind zinc. Upon Zn coordination, the classical ZFs fold into a structure made up of an α helix and an antiparallel β sheet. When folded, classical ZFs recognize and bind to specific DNA targets and function as transcription factors. With the advent of genome sequencing and proteomics, many additional classes of ZFs were identified based upon their primary amino acid sequences. At least 13 additional classes of ZFs are known, and collectively these “nonclassical” ZFs differ in the ligand set involved in Zn(II) coordination, the organization of the ligands within the polypeptide sequence and...