Structural Motifs in DNA-Binding Proteins

Zinc finger is a common structural motif in DNA-binding proteins. It is a hairpin bend of the protein held together by the Zn atom. 

Recall List three important structural motifs in DNA-binding proteins. 

Reflect and Apply Give examples of the major structural motifs in DNA-binding proteins, and explain how they bind. 

Another major structural motif found in DNA-binding proteins are zinc-mediated loops. So far, three classes of zinc modules have been recognized [111]. The common feature of these classes is the use of a zinc ion as a crosslink to stabilize a small... 

Figure 8.3 The DNA-binding protein Cro from bacteriophage lambda contains 66 amino acid residues that fold into three a helices and three P strands, (a) A plot of the Ca positions of the first 62 residues of the polypeptide chain. The four C-terminal residues are not visible in the electron density map. (b) A schematic diagram of the subunit structure. a helices 2 and 3 that form the helix-turn-helix motif ate colored blue and red, respectively. The view is different from that in (a), [(a) Adapted from W.F. Anderson et al., Nature 290 754-758, 1981. (b) Adapted from D. Ohlendorf et al., /. Mol. Biol. 169 757-769, 1983.]...

The presence of this common helix-turn-helix motif poised for DNA binding in lambda Cro and repressor provided considerable stimulus for further genetic and structural studies of these and other procaryotic DNA-binding proteins. All the results essentially supported the proposed mode of binding between these regulator proteins and DNA. 

Figure 9.8 Schematic diagram of the three-dimensional structure of the Antennapedia homeodomain. The structure is built up from three a helices connected by short loops. Helices 2 and 3 form a helix-turn-hellx motif (blue and red) similar to those in procaryotic DNA-binding proteins. (Adapted from Y.Q. Qian et al.. Cell 59 573-580, 1989.)...

A leucine zipper is a structural motif present in a large class of transcription factors. These dimeric proteins contain two extended alpha helices that grip the DNA molecule much like a pair of scissors at adjacent major grooves. The coiled-coil dimerization domain contains precisely spaced leucine residues which are required for the interaction of the two monomers. Some DNA-binding proteins with this general motif contain other hydrophobic amino acids in these positions hence, this structural motif is generally called a basic zipper. 

Zinc, in addition to its use as a Lewis acid in enzyme catalysis, plays a structural role in stabilizing protein molecules. It is also involved in a characteristic motif, termed zinc finger, in a number of eukaryotic DNA-binding proteins (that regulate the transcription of DNA into RNA), first described by Aaron Klug. 

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. 

P-sheet structures as DNA-binding motifs are found in pro- and eucaryotic DNA-binding proteins. As an example, the structure of the MetJ repressor from E. coli is shown in Fig. 1.9. The DNA is contacted in the major groove by the protruding P-strands. 

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