Sequence specificity major-minor groove binding proteins

Most sequence-specific regulatory proteins bind to their DNA targets by presenting an a helix or a pair of antiparallel p strands to the major groove of DNA. Recognition of the TATA box by TBP is therefore exceptional it utilizes a concave pleated sheet protein surface that interacts with the minor groove of DNA. Since the minor groove has very few sequence-specific... 

In conclusion, one important factor that contributes to the strong affinity of TBP proteins to TATA boxes is the large hydrophobic interaction area between them. Major distortions of the B-DNA structure cause the DNA to present a wide and shallow minor groove surface that is sterically complementary to the underside of the saddle structure of the TBP protein. The complementarity of these surfaces, and in addition the six specific hydrogen bonds between four side chains from TBP and four hydrogen bond acceptors from bases in the minor groove, are the main factors responsible for causing TBP to bind to TATA boxes 100,000-fold more readily than to a random DNA sequence. 

Figure 9.19 shows the sequence of the DNA that was used for the structure determination of the p53-DNA complex the bases involved in sequence-specific binding to the protein are shaded. One molecule of the DNA-bind-ing domain of p53 binds to the minor and the major grooves of the DNA making sequence-specific interactions with both strands (Figure 9.20). 

There is one complete twist of the helix every 10 base pairs, or 3.4 nm. This distance is referred to as the pitch of the helix. The surface of the heUx shows alternating major and minor grooves that follow the twist of the double-stranded molecule along its entire length. The major groove accommodates interactions with proteins (transcription factors see Chaps. 7 and 9) that recognize and bind to specific nucleotide sequences. 

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