N-terminal DNA binding domain

The x-ray structure of the N-terminal DNA-binding domain of the lambda repressor was determined to 3.2 A resolution in 1982 by Carl Pabo at Harvard University and revealed a structure with striking similarities to that of Cro, although the p strands in Cro are replaced by a helices in repressor. 

The 434 Cro molecule contains 71 amino acid residues that show 48% sequence identity to the 69 residues that form the N-terminal DNA-binding domain of 434 repressor. It is not surprising, therefore, that their three-dimensional structures are very similar (Figure 8.11). The main difference lies in two extra amino acids at the N-terminus of the Cro molecule. These are not involved in the function of Cro. By choosing the 434 Cro and repressor molecules for his studies, Harrison eliminated the possibility that any gross structural difference of these two molecules can account for their different DNA-binding properties. 

Figure 2. Structural and functional domains of PARP-1. PARP-1 has a highly conserved structural and functional organization including (1) an N-terminal DNA binding domain with two Cys-Cys-His-Cys zinc finger motifs (FI and Fll), (2) a nuclear localization signal (NLS), (3) a central automodification domain containing a BRCT ( BRCAl C-terminus-like ) protein-protein interaction motif, and (4) a C-terminal catalytic domain with a contiguous 50 amino acid sequence, the PARP signature motif, that forms the active site...

Each of the monomeric proteins c-jun and c-fos, as well as other members of the leucine zipper family, has an N-terminal DNA-binding domain rich in positively charged basic amino acid side chains, an activation domain that can interact with other proteins in the initiation complex, and the leucine-rich dimerization domain.363 The parallel coiled-coil structure (Fig. 2-21) allows for formation of either homodimers or heterodimers. However, cFos alone does not bind to DNA significantly and the cjun/cFos heterodimer binds much more tightly than does cjun alone.364 The yeast transcriptional activator protein GCN4 binds to the same 5 -TGACTCA sequence as does the mammalian AP-1 and also has a leucine zipper structure.360 364 365... 

Fig. 8. Model for the Cu-induced inactivation of Mac 1. Experiments suggest that Cu(I) binding to the Cl motif induces an intramolecular interaction between the N-terminal DNA-binding domain and the C-terminal Cu-binding modules, resulting in an inactive Mad. The Cu-regulatory domain of Mad is shown at the bottom with the candidate ligands shown in large font. This motif binds four Cu(I) ions, and a postulated tetracopper cluster is shown.

Engineered mutations in the second Cys-rich motif did not yield a consti-tutively active Mad. These results are consistent with the Cl motif being the major Cu-regulatory switch. Both Cys-rich motifs exhibited transactivation activity, although the Cl activator was weak relative to the C2 activator (Keller et al., 2000). Limited copper metalloregulation of Mad was observed with only the Cl activator fused to the N-terminal DNA-binding domain. Thus, the two Cys-rich motifs appear to function independently. The Cl Cys-rich motif appears to be a functional copper-regulatory domain, whereas the C2 motif is the major transactivator. 

The winged helix family. A group of large protein transcription factors contain an N-terminal DNA-binding domain with the striking winged helix mohf shown in Fig. It occurs in proteins from a... 

---