A CONSENSUS ZINC FINGER PEPTIDE - DESIGN, HIGH-AFFINITY METAL-BINDING, A PH-DEPENDENT STRUCTURE, AND A HIS TO CYS SEQUENCE VARIANT

A single zinc finger peptide, ProTyrLysCysProGluCysGlyLysSerPheSerGlnLysSerAspLeuValLysHisGlnArgThrHisThrGly, has been designed with the use or a data base of 131 zinc ringer sequences. Studies indicated that this peptide binds metal ions such as Zn2+ and Co2+ and folds in their presence. The affinity of this peptide for metal ions is greater than that demonstrated for any other zinc finger peptide characterized to date. Nuclear magnetic resonance studies revealed that the zinc complex of this peptide adopts a structure similar to that predicted and observed for other zinc finger domains. In addition, these studies led to the discovery that the latter of the histidine residues can be protonated and dissociated from the metal center with only local loss of structure. This histidine residue can also be replaced with a cysteine residue to yield a peptide that has a (Cys)3(His) rather than a (Cys)2(His)2 metal binding site.