Motif DNA binding

Figure 2.12 Two a helices that are connected by a short loop region in a specific geometric arrangement constitute a helix-turn-helix motif. Two such motifs are shown the DNA-binding motif (a), which is further discussed in Chapter 8, and the calcium-binding motif (b), which is present in many proteins whose function is regulated by calcium.

Both lambda Cro and repressor proteins have a specific DNA-binding motif... 

The specific arrangement of two a helices joined by a loop region in lambda Cro and repressor, as well as in CAP, constitute the helix-turn-helix DNA-binding motif (Figure 8.8), which also occurs in some eucaryotic transcription factors as discussed in Chapter 9. The orientation of the two helices and... 

Brennan, R.G., Matthews, B.W. The helix-turn-helix DNA-binding motif. /. Biol. Chem. 264 1903-1906, 1989. 

The DNA-binding motifs discussed in this and the preceding two chapters are those most frequently found in procaryotes and eucaryotes. However, other motifs are known, for example the p sheet motif of the met repressor in Escherichia coli which binds to the major groove of DNA. No doubt others remain to be discovered. 

Dimerization of the Ce-zinc cluster transcription factors involves an a-helical coiled coil in the dimerization region. Coiled coils, often called leucine zippers, are also found in a large group of transcription factors that do not contain zinc. The leucine zipper is made up of two a helices in a coiled coil with every seventh residue leucine or some other large hydrophobic residue, such as isoleucine or valine. Leucine zipper transcription factors (b/zip) include factors characterized by heterodimerization, for example Fos and Jun. The a-helical DNA-binding motifs of the heterodimers recognize quite different base sequences and are continous with the a helices of the zipper. 

A helix-loop-helix motif is a DNA-binding motif, related to the leucine-zipper. A helix-loop-helix motif consists of a short a helix, connected by a loop to a second, longer a helix. The loop is flexible and allows one helix to fold back and pack against the other. The helix-loop-helix structure binds not only DNA but also the helix-loop-helix motif of a second helix-loop-helix protein forming either a homodimer or a heterodimer. 

Fig. 3.4 Polyamide-DNA binding motifs with equilibrium association constants K,). Hairpin amino-substitution at the a-position of the y-turn residue leads to enhanced binding affinity (10-fold) without loss of specificity, and with higher orientational selectivity and offers potential for further substitution. Cycle Cyclic polyamides show higher affinity than analogous hairpin molecules with the same number of cationic groups and eliminate all possibility of extended 1 1 binding. H-pin and U-pin compared to their non-linked analogs, H-pins and U-pins exhibit higher binding affinity. The black and open circles represent Im and Py rings, respectively diamonds repre-...

Fig. 3.6 Polyamide-DNA binding motifs targeting longer DNA sequences. Overlapped and slipped homodimers depending on the sequence context, six-ring polyamides with central p-Ma residues can bind to DNA as fully overlapped homodimers, recognizing 11 bp, or as slipped homodimers, recognizing 13 bp. Extended hairpin extended conformation increases binding site size (to 9 bp) and enhances binding affinity. Cooperative dimer a cooperatively binding hairpin polyamide can...

Tab. 3.1 DNA-binding proteins that have been inhibited by polyamides. The known DNA binding motifs from NMR or crystal structure data are shown. Significant groove contacts and proposed mechanism of polyamide inhibition are also shown for each protein...

Transcription factor DNA-binding motif Groove recognition Proposed mechanism of inhibition... 

HhHl Helix-hairpin-helix DNA-binding motif class 1 E(MFP)AB 2(2) 2(3) 1BDX... 

DNA-binding proteins contact their recognition sequences via defined structural elements, termed DNA-binding motifs (overview Pabo Sauer, 1992 Burley, 1994). DNA-binding motifs are often found in structural elements of the protein which can fold independently from the rest of the protein and therefore represent separate DNA-binding domains. They can, however, also occur within sequence elements which can not independently fold, but whose folding depends on the tertiary structure of the rest of the protein. 

---