Binding Motifs with Zinc Ions

The first zinc binding motif discovered was that of the eucaryotic transcription factor TFIIIA of Xenopus laevis which contains 9 copies of a Cys2His2-Zinc motif The structure of the binding motif is shown in Fig. 1.4. The central zinc ion serves to pack an a-hehx against a P-sheet and thereby position the a-helix. The recognition of the DNA sequence occurs via this a-helix. 

The zinc binding element plays, above aU, a structuring role by ensuring that the recognition hehx is correctly oriented and stabUized. The zinc ion does not contact the DNA directly. In Zif268 the zinc motif participates directly in the DNA-binding via formation of a H-bond between the His residue of the zinc complex and the N7 of a G C base pair of the DNA. 

The DNA-binding of the steroid hormone receptor occurs via an approx. 60 amino acid DNA-binding domain with two zmc-Cys4-motrfs (see also 4.3.2). The structure displays two so-called helix-loop-hehx elements, each with a boimd Zn ion (Fig. 1.6). 

Both zinc ions are each complexed by 4 Cys residues, whereby a non-equivalent arrangement of the two Zn ions is observed. The binding specificity is accomplished by amino acid residues near the N-terminus of the first helix in a hehx-loop-hehx element. 

Here two zinc ions are complexed by 6 Cys residues, whereby two of the Cys residues bind to both ligands (see Fig. 1.3 Fig. 1.4). The structure of GAL4 complexed with its recognition sequence indicates that the Zn ions mainly act to stabilize the small globular GAL4 protein and to orient the recognition helix correctly within the major groove. 

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Alternatively, certain sequences associated with particular structural motifs (Chapter 4) may be identified within a protein. The presence of a structural motif may suggest that it, say, catalyzes ATP hydrolysis, binds to DNA, or forms a complex with zinc ions, helping to define molecular function. These relationships are determined with the aid of increasingly sophisticated computer programs, limited only by the current information on gene and protein structure and our capacity to associate sequences with particular structural motifs. 

The biphenyl ligand functionalized with two imidazoles (6) was used to produce distorted tetrahedral complexes of zinc.119 2,2 -Biimidazole can act as a bidentate ligand coordinating to one zinc ion (7) or as a bridging ligand in the formation of dimeric species (8) with X-ray structures of both binding motifs.120... 

Figure 12.14 (Left) Schematic representation of tandemly repeated zinc finger motif with their tetrahedrally coordinated Zn2+ ions. Conserved amino acids are labelled, and the most probable DNA-binding side chains are indicated by balls (from Klug and Rhodes, 1988). (Right) A ribbon diagram of a single zinc finger motif in a ribbon diagram representation. (From Voet and Voet, 2004. Reproduced with permission from John Wiley Sons., Inc.)...

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