title: Cysteine and histidine shuffling: mixing and matching cysteine and histidine residues in zinc finger proteins to afford different folds and function.
abstract: Zinc finger proteins utilize zinc for structural purposes: zinc binds to a combination of cysteine and histidine ligands in a tetrahedral coordination geometry facilitating protein folding and function. While much is known about the classical zinc finger proteins, which utilize a Cys(2)His(2) ligand set to coordinate zinc and fold into an anti-parallel beta sheet/alpha helical fold, there are thirteen other families of 'non-classical' zinc finger proteins for which relationships between metal coordination and protein structure/function are less defined. This 'Perspective' article focuses on two classes of these non-classical zinc finger proteins: Cys(3)His type zinc finger proteins and Cys(2)His(2)Cys type zinc finger proteins. These proteins bind zinc in a tetrahedral geometry, like the classical zinc finger proteins, yet they adopt completely different folds and target different oligonucleotides. Our current understanding of the relationships between ligand set, metal ion, fold and function for these non-classical zinc fingers is discussed.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland 21201-1180, USA.
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Michalek
authors.forename: Angelique N
authors.initials: AN
authors.lastname: Besold
authors.forename: Sarah L J
authors.initials: SL
authors.lastname: Michel
mesh_terms: D000595:Amino Acid Sequence; D003545:Cysteine / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry*; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D016415:Sequence Alignment; D015032:Zinc / Q000737:chemistry; D016335:Zinc Fingers
chemical_list: D011506:Proteins; D006639:Histidine; D015032:Zinc; D003545:Cysteine